ARYL BENZOYL IMIDAZOLE COMPOUNDS FOR THE TREATMENT OF LUNG CANCER CROSS-REFERENCE TO RELATED APPLICATION [001] This application claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application serial number 62/894,524, filed August 30, 2019, and is incorporated herein by reference in its entirety. GOVERNMENT INTEREST STATEMENT [002] This invention was made in whole or in part with government support under Grant Number R01CA148706, awarded by the National Institutes of Health. The government may have certain rights in the invention. BACKGROUND OF THE INVENTION [003] Despite the extensive research and a wide range of viable treatment modalities, lung cancer related mortality has steeply risen over the decades. It has been estimated that lung cancer related death is expected to be the highest among all cancers in the United States in 2018 without sex disparity. Non-small-cell lung cancer (NSCLC) accounts for the major subtype and involves more than 85% of cases among all lung cancer that characterizes into adenocarcinoma, and squamous and large-cell undifferentiated carcinoma. The treatment for lung cancer has changed dramatically since the discovery of genetic mutations that led to newer therapeutic agents as targeted therapy. Response to different chemotherapeutic agents depended on the histological subtypes including the origin or types of tissue, mutation on the gene, and also resistance to drug therapy. Thus, new therapeutic agents were introduced to the market since the hallmarks of the tumor microenvironment and molecular alterations began to be understood. Despite the histological subtype, all the patients from NSCLC in the early 90’s received the same combination of chemotherapies that included platinum doublet regimens with either taxanes (paclitaxel or docetaxel) or antimetabolites (e.g., gemcitabine). The target-independent cytotoxic drugs were shown to be effective at the first year of treatment as they increased the overall survival of stage IIIB-IV NSCLC patients. Together with lung cancer, cytotoxic drugs, including paclitaxel, are widely used in the treatment of various cancers including pancreatic, breast, and ovarian cancers. [004] Microtubule targeting agents (MTAs) have received considerable interest in cancer treatment as they disrupt the proliferating tumor cells by stabilizing or destabilizing the microtubule dynamics. Targeting microtubules in cancer cells is an important chemotherapeutic treatment strategy that leads to cell cycle arrest in G2/M phase and subsequent cell death. Among various MTAs, taxanes are known to occupy binding sites in the ^ subunit of ^/^ tubulin and are approved against various solid tumors including NSCLC. However, the lack of therapeutic efficacy in later stage cancer treatment, because of acquired or intrinsic resistance, has emerged as a key barrier for successful treatment of MTAs. Overexpression of multidrug resistance (MDR) protein is a hallmark of most solid tumors that leads to treatment failure and uncontrolled disease progression. Accumulating evidence suggests that P-glycoprotein (P-gp), which is an ATP-binding cassette (ABC) transporter, may decrease the intracellular drug accumulation resulting in low drug cytotoxicity towards tumor cells. Other resistance mechanisms include the upregulation of drug export pump multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein 1 (BCRP1), altered expression of tubulin isotypes, and mutations in the b-tubulin gene. Paclitaxel is a known substrate for P-gp transmembrane protein. To reverse MDR, several past efforts to develop ideal P-gp inhibitors have failed or been discontinued during clinical trials. For example, verapamil and cyclosporine A are two well-known substrates for P-gp, but they are indicated under different physiological conditions to result in side effects. Other newer P-gp modulators have also been found to be ineffective in clinical trials. [005] Microtubules are the essential cellular components and fundamentally responsible for structural scaffolds, mitosis, cellular transport, and intracellular signaling. Microtubules possess highly dynamic instability and vary during cell division, thus making them an attractive target for the treatment of various locally advanced cancers. A class of chemotherapeutics known as microtubule binding agents, widely used in different malignancies, are derived from natural sources. For example, paclitaxel, a widely used chemotherapeutic, acts as a microtubule-stabilizing agent by binding to the inner surface of the ^ subunit of tubulin. Although taxanes, such as paclitaxel and docetaxel, have served as an important treatment strategy for decades in lung, breast, and ovarian cancer, paclitaxel therapy has become ineffective due to increased drug resistance and drug target mutation. There is strong clinical evidence that ^III-tubulin is expressed at high levels in various taxane-resistant cancers that are often associated with other clinical manifestations such as high grade, aggressive metastatic cancer having poor prognosis due to undifferentiated cancer cells. In NSCLC, paclitaxel-resistant cells also demonstrate an abundant expression of bIII-tubulin compared with its sensitive counterpart. [006] In parallel to therapeutic resistance, taxanes have dose limiting toxicity such as neurotoxicity and hematologic toxicity. Moreover, they require formulation with solubilizer (Cremophor EL) due to their low aqueous solubility, which caused severe hypersensitive reactions in patients. In order to overcome therapy associated treatment resistance, a newer generation of tubulin inhibitors is urgently needed to substitute the existing drugs and manage their detrimental adverse effects in patients with NSCLC and other tumor types. SUMMARY OF THE INVENTION [007] In one embodiment, the invention encompasses methods of treating lung cancer in a subject comprising administering a therapeutically effective amount of a compound of Formula XI to the subject, wherein Formula XI is represented by: wherein X is a bond, NH or S; Q is O, NH or S; and A is a ring and is a substituted or unsubstituted saturated or unsaturated single-, fused- or multiple-ring, aryl or (hetero)cyclic ring system; N-heterocycle; S-heterocycle; O-heterocycle; cyclic hydrocarbon; or mixed heterocycle; wherein the A ring is optionally substituted by 1-5 substituents which are independently O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, -CH ₂ CN, NH ₂ , hydroxyl, - (CH ₂ ) _i NHCH ₃ , -(CH ₂ ) _i NH ₂ , -(CH ₂ ) _i N(CH ₃ ) ₂ , -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O- alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; i is an integer between 0-5; wherein if Q is S, then X is not a bond, or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [008] Another embodiment of the invention encompasses methods of treating lung cancer in a subject in need thereof by administering a therapeutically effective amount of a compound of Formula VIII to the subject, wherein Formula VIII is represented by the structure: wherein, R ₄ , R ₅ and R ₆ each independently is hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ ) _i NHCH ₃ , -(CH ₂ ) _i NH ₂ , -(CH ₂ ) _i N(CH ₃ ) ₂ , - OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO- alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; Q is S, O or NH; i is an integer between 0-5; and n is an integer between 1-3; or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [009] Yet another embodiment of the invention encompasses methods of treating lung cancer in a subject in need thereof by administering a therapeutically effective amount of a compound of Formula XI(b) to the subject, wherein Formula XI(b) is represented by the structure: wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; i is an integer from 0-5; and n is an integer between 1-4; or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0010] One embodiment of the invention encompasses methods of treating lung cancer in a subject in need thereof by administering a therapeutically effective amount of a compound of Formula XI(c) to the subject, wherein the compound of Formula XI(c) is represented by the structure: wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; i is an integer from 0-5; and n is an integer between 1-4; or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0011] Another embodiment of the invention encompasses methods of treating lung cancer in a subject in need thereof by administering a compound of Formula XI(e), wherein Formula XI(e) is represented by the structure: wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ ) _i NHCH ₃ , -(CH ₂ ) _i NH ₂ , -(CH ₂ ) _i N(CH ₃ ) ₂ , - OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO- alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; i is an integer from 0-5; and n is an integer between 1-4; or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0012] Yet another embodiment of the invention encompasses methods of treating lung cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of at least one of the following compounds: (2-(phenylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (5a), (2-(p-tolylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (5b), (2-(p-fluorophenylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (5c), (2-(4-chlorophenylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (5d), (2-(phenylamino)-1H-imidazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (5e), 2-(1H-indol-3-yl)-1H-imidazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (17ya); and (2-(1H-indol-5-ylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone (55) or pharmaceutically acceptable salts of these compounds. [0013] In another embodiment, the compound of this invention is its stereoisomer, pharmaceutically acceptable salt, hydrate, N-oxide, or combinations thereof. The invention includes pharmaceutical compositions comprising a compound of this invention and a pharmaceutically acceptable carrier. BRIEF DESCRIPTION OF THE DRAWINGS [0014] The subject matter regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of the specification. The invention, however, both as to organization and method of operation, together with objects, features, and advantages thereof, may best be understood by reference to the following detailed description when read with the accompanying drawings in which: [0015] Figures 1A-1E illustrate the cytotoxic effects of Compound 17ya as evaluated by MTS assay to determine the cell viability on various lung cancer cell lines. Figure 1A illustrates results of the cytotoxic test of Compound 17ya, colchicine, and paclitaxel on H1299 cell line after 72 h treatment. Figure 1B illustrates results of the cytotoxic test of Compound 17ya, colchicine, and paclitaxel on HCC827 cell line after 72 h treatment. Figure 1C illustrates results of the cytotoxic test of Compound 17ya, colchicine, and paclitaxel on H460 cell line after 72 h treatment. Figure 1D illustrates results of the cytotoxic test of Compound 17ya, colchicine, and paclitaxel on A549 cell line after 72 h treatment. Figure 1E illustrates results of the cytotoxic test of Compound 17ya, colchicine, and paclitaxel on A549/TxR cell line after 72 h treatment. [0016] Figure 2 illustrates the cell proliferation and migration effects of Compound 17ya on A549 and A549/TxR cell lines with a representative image from the colony formation assay. [0017] Figures 3A-3D illustrate the effect of the compounds on cell proliferation and cell migration. Figure 3A illustrates the bar graph representation of the quantification of the result from colony area in A549 cells, when the experiment was conducted using two different drug concentrations (4nM and 16nM) in 6-well plate, where ImajeJ software was used to calculate the total colony occupied area. Figure 3B illustrates the bar graph representation of the quantification of the result from colony area in A549/TxR cells, when the experiment was conducted using two different drug concentrations (4nM and 16nM) in 6-well plate, where ImajeJ software was used to calculate the total colony occupied area. Figure 3C illustrates the graphical representation of wound healing assay done in 12-well plate format and the drug solutions were incubated for 36 hours to observe the effect of Compound 17ya as compared with positive controls colchicine and paclitaxel with A549 cells, where the total scratched area that covered with migrated cells was quantified and represented as percent of total wound closure area and the data is presented as mean ± SEM of triplicates and the Kruskal-Wallis test was performed for the statistical significance. *P<0.05, **P<0.01 versus control or indicated. Figure 3D illustrates the graphical representation of wound healing assay done in 12-well plate format and the drug solutions were incubated for 36 hours to observe the effect of Compound 17ya as compared with positive controls colchicine and paclitaxel with A549/TxR cells, where the total scratched area that covered with migrated cells was quantified and represented as percent of total wound closure area and the data is presented as mean ± SEM of triplicates and the Kruskal- Wallis test was performed for the statistical significance. *P<0.05, **P<0.01 versus control or indicated. [0018] Figure 4A-4C illustrate the effect of Compound 17ya on cell invasion on A549 and A549/TxR cell lines. Figure 4A illustrates the effect of Compound 17ya on cell invasion in A549 and A549/TxR cell lines with the images showing the invaded cells after control or treatment with Compound 17ya, colchicine, or paclitaxel from the matrigel coated surface with the scale bar = 200 µm. Figure 4B illustrates the relative number of A549 cells compared with control invaded from apical to basolateral side and the data is presented as mean ± SEM with a Kruskal-Wallis test performed for the statistical significance where *P<0.05, **P<0.01 versus control or indicated. Figure 4C illustrates the relative number of A549/TxR cells compared with control invaded from apical to basolateral side and the data is presented as mean ± SEM with a Kruskal-Wallis test performed for the statistical significance where *P<0.05, **P<0.01 versus control or indicated. [0019] Figures 5A-5E illustrate the effect of Compound 17ya on the bypass of efflux transporter in P-gp overexpressed resistant cell line. Figure 5A illustrates the effect of Compound 17ya on the absorption of rhodamine-123, a substrate for P-gp, that had a lower accumulation in resistant cells (A549/TxR) than in A549 cells as determined by flow cytometry. Figure 5B illustrates the effect of verapamil, another positive substrate for P-gp, that blocks the efflux transporter and thereby increased accumulation of rhodamine-123 into the A549/TxR cells. Figure 5C illustrates the comparison of rhodamine-123 accumulation in the presence of verapamil and Compound 17ya in A549 cell line. Figure 5D illustrates the comparison of rhodamine-123 accumulation in the presence of verapamil and Compound 17ya in A549/TxR cell line. The data is presented as mean ± SEM of triplicates and the unpaired t test with Welch’s correction was performed for the statistical significance. *P<0.05, **P<0.01 versus control or indicated. [0020] Figures 6A-6D illustrate the effect of Compound 17ya on inducing the cell death in A549 and A549/TxR cells where the cells were fixed with 70% ethanol and treated with RNase. Figure 6A illustrates the effect on cell death of A549 cell line of the control, paclitaxel, colchicine, and Compound 17ya as determined by flow cytometry (FACS) analysis using Propidium iodide (PI) staining showed the cell cycle arrest in G2/M phase after adding 100 nM drug concentration for 24 h time. Figure 6B illustrates the effect on cell death of A549/TxR cell line of the control, paclitaxel, colchicine, and Compound 17ya as determined by flow cytometry (FACS) analysis using PI staining showed the cell cycle arrest in G2/M phase after adding 100 nM drug concentration for 24 h time. Figure 6C illustrates the quantitative analysis of Figure 6A. Figure 6D illustrates the quantitative analysis of Figure 6B. [0021] Figure 7A-7F illustrate the antitumor efficacy of Compound 17ya in A549 and A549/TxR xenograft models. Figure 7A illustrates the tumor volume over time of A549 xenografted mice dosed with a control, Compound 17ya (7.5 mg/kg and 12.5 mg/kg, oral gavage), or paclitaxel (12.5 mg/kg i.p.) where significant inhibition of tumor growth occurred within all treated groups. Figure 7B illustrates the body weight of the A549 xenografted mice dosed with a control, Compound 17ya (7.5 mg/kg and 12.5 mg/kg, oral), or paclitaxel (12.5 mg/kg, i.p.). Figure 7C illustrates the tumor weight of A549 xenografted mice dosed with a control, Compound 17ya (7.5 mg/kg and 12.5 mg/kg, oral), or paclitaxel (12.5 mg/kg i.p.), which was significantly lower than in the control sample. Figure 7D illustrates a xenograft study showing A549/TxR resistant tumor volume after treatment with control, paclitaxel (12.5 mg/kg, i.p.), Compound 17ya (7.5 or 12.5 mg/kg, oral), cisplatin (injected at a dose of 5 mg/kg ip once in a week) and the combination group received 12.5 mg/kg po of Compound 17ya and 5 mg/kg ip of cisplatin. Figure 7E illustrates the mice body weight after treatment with control, paclitaxel (12.5 mg/kg), Compound 17ya (7.5 or 12.5 mg/kg), cisplatin (injected at a dose of 5 mg/kg ip once in a week) and the combination group received 12.5 mg/kg po of Compound 17ya and 5 mg/kg ip of cisplatin. Figure 7F illustrates the quantitative analysis for tumor weight of mice after treatment with control, paclitaxel (12.5 mg/kg), Compound 17ya (7.5 or 12.5 mg/kg), cisplatin (injected at a dose of 5 mg/kg ip once in a week) and the combination group received 12.5 mg/kg po of Compound 17ya and 5 mg/kg ip of cisplatin. Data represented as the mean±SEM (n=5-7). Statistical analysis was performed by Dunnett multiple comparison test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 versus control or indicated. [0022] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. DETAILED DESCRIPTION OF THE PRESENT INVENTION [0023] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention. [0024] Development of tubulin inhibitors that are as potent as paclitaxel and may overcome the taxane resistance in lung cancer is important. Unlike taxanes, Compound 17ya and its analogs bind with the colchicine binding site and thereby promote depolymerization of microtubules. Mounting evidence suggests that colchicine binding agents show several advantages over other tubulin inhibitors such as being less prone to ABC efflux transporters, higher water solubility, and low molecular weight, which contribute to enhanced oral bioavailability. In particular, Compound 17ya is reported to have high oral bioavailability (21 ~ 50 %) in both small and large animal models. [0025] Compound 17ya and other 2^Aryl-4-benzoyl-imidazoles are potent tubulin inhibitors that destabilize microtubules and have been found to be effective in P-gp overexpressed cell lines in both cell culture and animal studies. Unlike paclitaxel and vinorelbine, the new compounds specifically bind with the colchicine binding site in tubulin and thus lower the chance as a potential substrate for MDR protein. Not to be limited by theory, it is believed that the invention is based in part on 2-Aryl-4-benzoyl-imidazoles effective against lung cancer. Different in-vitro experiments using sensitive and resistant lung cancer cell lines proved the efficacy of 2-Aryl-4-benzoyl-imidazoles as tubulin inhibitors under lung cancer conditions. In addition, orally administered 2^Aryl-4-benzoyl- imidazoles were shown to be effective in xenograft tumor model compared with paclitaxel therapy. [0026] Unlike taxane, Compound 17ya and its analogs are orally available and have several advantages over conventional maximum tolerated dose (MTD) based intravenous drugs. The advantages include, but are not limited to, prolonged plasma drug concentration, reduced toxicity, and convenient frequent dosing. In xenograft studies, oral administration of Compound 17ya showed significant tumor reduction in both A549 and A549/TxR cell lines. Compound 17ya treated mice exhibited normal body weight indicating the drug therapy was safe. [0027] It is important to note that paclitaxel therapy is often associated with dose limiting toxicity such as neurotoxicity and myelosuppression, among other adverse effects. In resistant tumors, paclitaxel could not suppress tumor growth of A549/TxR cells. In most cases, treatment of lung cancer relies on the use of a combination of chemotherapeutics. Consequently, cisplatin therapy was tested in combination with Compound 17ya and the results indicated that the combination therapy was the most effective in controlling the tumor growth among all other treatment groups. Compound 17ya showed superior anti-cancer activity as a single agent or in-combination with other cytotoxic drugs in sensitive and taxane-resistant lung cancer models. [0028] The invention encompasses methods of treating lung cancer by administering at least one compound of formula (XI) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula (XI) is represented by the structure: [0029] wherein [0030] X is a bond, NH or S; [0031] Q is O, NH or S; and [0032] A is substituted or unsubstituted single-, fused- or multiple-ring aryl or (hetero)cyclic ring systems; substituted or unsubstituted, saturated or unsaturated N-heterocycles; substituted or unsubstituted, saturated or unsaturated S-heterocycles; substituted or unsubstituted, saturated or unsaturated O-heterocycles; substituted or unsubstituted, saturated or unsaturated cyclic hydrocarbons; or substituted or unsubstituted, saturated or unsaturated mixed heterocycles; wherein said A ring is optionally substituted by 1-51-5 substituents which are independently O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; and [0033] i is an integer from 0-5; [0034] or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0035] In one embodiment if Q of Formula XI is S, then X is not a bond. [0036] In one embodiment, A of compound of Formula XI is Ph. In another embodiment, A of compound of Formula XI is substituted Ph. In another embodiment, the substitution is 4-F. In another embodiment, the substitution is 4-Me. In another embodiment, Q of compound of Formula XI is S. In another embodiment, X of compound of Formula XI is NH. Non limiting examples of compounds of Formula XI are selected from: (2- (phenylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methanone (5a), (2-(p- tolylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methanone (5b), (2-(p- fluorophenylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)metha none (5c), (2-(4- chlorophenylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)metha none (5d), (2- (phenylamino)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl)metha none (5e), (2- (phenylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methanone hydrochloride salt (5Ha), (2-(p-tolylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methan one hydrochloride salt (5Hb), (2-(p-fluorophenylamino)thiazol-4-yl)(3,4,5-trimethoxyphenyl )methanone hydrochloride salt (5Hc), (2-(4-chlorophenylamino)thiazol-4-yl)(3,4,5- trimethoxyphenyl)methanone hydrochloride salt (5Hd), (2-(phenylamino)-1H-imidazol-4- yl)(3,4,5-trimethoxyphenyl)methanone hydrochloride salt (5He) and pharmaceutically acceptable salts thereof. [0037] The invention also encompasses methods of treating lung cancer by administering at least one compound of formula XI(a) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula XI(a) is represented by the structure: [0038] wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, - NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; [0039] i is an integer from 0-5; and [0040] n is an integer between 1-4; [0041] or an isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0042] The invention also encompasses methods of treating lung cancer by administering at least one compound of formula XI(b) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula XI(b) is represented by the structure: [0043] wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ ) _i NHCH ₃ , -(CH ₂ ) _i NH ₂ , -(CH ₂ ) _i N(CH ₃ ) ₂ , -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, - NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; [0044] i is an integer from 0-5; and [0045] n is an integer between 1-4; [0046] or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0047] The invention also encompasses methods of treating lung cancer by administering at least one compound of formula XI(c) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula XI(c) is represented by the structure: [ [0049] wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, - NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; [0050] i is an integer from 0-5; and [0051] n is an integer between 1-4; [0052] or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0053] The invention also encompasses methods of treating lung cancer by administering at least one compound of formula XI(d) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula XI(d) is represented by the structure: [ [0055] wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ ) ₂ , -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, - NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; [0056] i is an integer from 0-5; and [0057] n is an integer between 1-4; [0058] or an isomer, pharmaceutically acceptable salts, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof. [0059] The invention also encompasses methods of treating lung cancer by administering at least one compound of formula XI(e) in a therapeutically effective amount to a subject in need thereof, wherein the compound of Formula XI(e) is represented by the structure:

[0060] wherein R ₄ and R ₅ are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF ₃ , CN, -CH ₂ CN, NH ₂ , hydroxyl, -(CH ₂ )iNHCH ₃ , -(CH ₂ )iNH ₂ , -(CH ₂ )iN(CH ₃ )2, -OC(O)CF ₃ , C ₁ -C ₅ linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH ₂ Ph, - NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH ₂ or NO ₂ ; [0061] i is an integer from 0-5; and [0062] n is an integer between 1-4; [0063] or its pharmaceutically acceptable salt, hydrate, polymorph, metabolite, tautomer or isomer. [0064] The invention also encompasses methods of treating lung cancer by administering compound 55 or a pharmaceutically acceptable salt thereof in a therapeutically effective amount to a subject in need thereof, wherein compound 55 is represented by the structure: [0065] The invention also encompasses methods of treating lung cancer by administering compound 17ya or a pharmaceutically acceptable salt thereof in a therapeutically effective amount to a subject in need thereof, wherein compound 17ya is represented by the structure:

[0066] Compound 17ya demonstrated potent cytotoxicity in lung cancer cells including taxane resistant subline. The cell viability assay was performed to assess the efficacy of Compound 17ya on different types of lung cancer cell lines. Compound 17ya showed similar efficacy in comparison with the colchicine treated cell lines as illustrated in Figures 1A-1E. Compound 17ya had excellent inhibitory activity in the nano-molar range against different phenotypes of lung cancer cell lines, such as, HCC827 (EGFR mutated epithelial adenocarcinoma), H1299 (P53 negative NSCLC), A549 (NSCLC), and H460 (P53 positive epithelial large cell carcinoma). Among three cytotoxic drugs: compound 17ya, paclitaxel, and colchicine, paclitaxel exhibited higher potency in all lung cancer cells (0.37- 19.08 nM). However, both paclitaxel and colchicine were ineffective in the taxane resistant cell line (A549/TxR) and the resistance index (RI) was 283.6 and 6.7, respectively (See, Table 1). In contrast, Compound 17ya showed equivalent potency to induce cell death on parenteral A549 and resistant A549/TxR cell lines with IC50 values of 55.6 nM and 102.9 nM, respectively. The resistance index between A549 and A549/TxR (RI) was only 1.85 (see Figures 1D and 1E). In general, p-gp has been over-expressed in many taxane-resistant cells. The results indicated that Compound 17ya may be a useful substitute for the existing tubulin inhibitors in the clinical treatment of taxane-resistant lung cancer. [0067] Compound 17ya inhibited the proliferation of lung cancer cells. When a small number cells were added to the culture plate, the cells started to proliferate and become a colony that enabled evaluation of the potential anti-proliferative effects of a drug candidate. The results revealed that Compound 17ya reduced new colony formation and suppressed cell growth for a longer period of time (10 days) in particular at concentrations of 16 nM. See Figure 2. In A549 cells, treatment with 4 nM and 16 nM concentrations of Compound 17ya covered 9.11% and 0.98% of the colony area. In contrast, the colonies from the control group occupied 15.94% of the total surface area. This is graphically represented in Figures 3A and 3B. The paclitaxel treated cell was most effective at stopping new colony formation that demonstrated partial growth inhibition at 4 nM and complete growth inhibition at 16 nM concentration. Both Compound 17ya and paclitaxel treatment groups at higher drug concentrations demonstrated comparable inhibitory effects of colony formation. The results were significant (p = 0.028 for Compound 17ya and p = 0.0029 for paclitaxel). In the case of A549/TxR cells, both paclitaxel and colchicine failed to control cell proliferation. In contrast, Compound 17ya inhibited colony formation (1.94%, p = 0.0023) in both of the lung cancer cell lines. [0068] Compound 17ya curbed invasion and migration of cancer cells. A wound healing assay revealed that Compound 17ya had comparable efficacy to inhibit the cell migration compared with paclitaxel, and had significantly higher efficacy compared with the colchicine treated group in sensitive A549 cells (p = 0.0286). After 36 hours, the control cell completely covered the scratch area, while treatment with Compound 17ya, paclitaxel, or colchicine demonstrated 50.34%, 47.78%, and 64.6% of wound closure from the initial scratch area, respectively. In contrast, positive control groups were unable to stop the migration process in A549/TxR cells. Compound 17ya demonstrated significantly higher wound closure capacity (50.89%, p = 0.002 vs. colchicine, and p = 0.0240 vs. paclitaxel) compared with the positive control treated groups. The results are illustrated in Figures 3C and 3D. [0069] The cell invasive capability of Compound 17ya was determined by using matrigel coated transwell membrane. After 48 hours of drug treatment, the invading cells from the lower chamber were stained and the images were quantified by ImageJ software. The results indicated that all of the three treatment groups showed marked inhibition of A549 cell invasion compared with the control. See Figure 4A. The results of Compound 17ya and paclitaxel were in agreement with the migration study and found to be statistically significant (p = 0.028 to Compound 17ya and p = 0.0025 to paclitaxel). In the case of a resistant cell line, treatment with Compound 17ya inhibited 33.06% of invaded cells while the capacity of paclitaxel and colchicine to suppress the cell invasion was very negligible as graphically illustrated in Figures 4B and 4C. [0070] The effect of Compound 17ya, a potent tubulin inhibitor, was tested in sensitive and resistant lung cancer cell lines. The cell viability assay demonstrated the comparable efficacy of Compound 17ya with paclitaxel and colchicine, and the IC ₅₀ value showed a range of 28.98 nM to 178 nM in four lung cancer lines. Then the compounds were tested against a drug resistance model. [0071] A549 cells were converted into taxane resistance cells by repeated exposure to low concentrations of paclitaxel in culture media for a prolonged time until drug resistance reached a desired level. MTS assay revealed that normal susceptibly towards paclitaxel therapy was completely lost and partially lost for colchicine. When tested Compound 17ya showed similar cell viability in sensitive and resistant A549 cells. Compound 17ya demonstrated dose-dependent inhibition of cell colony proliferation on both sensitive and resistant cell lines. In contrast, paclitaxel and colchicine therapy were not as effective in the A549/TxR cell line. All three drug treatments delayed migration of lung tumor cells in the wound healing assay, but failed in resistant cells except for Compound 17ya. [0072] Several experimental techniques for studying angiogenesis and metastasis of cancer cells were developed. Matrigel coated transwell chambers contained various extracellular matrices (ECM) and growth factors to study the invasiveness of lung cancer cell lines. The in-vitro data from the invasion assay showed that Compound 17ya reduced the quantity of cells crossing the porous membrane in the presence of a chemoattractant. The result indicated that compound 17ya drug therapy inhibited A549 cell metastasis. Compound 17ya also effectively controlled the cell invasion in the resistant cells A549/TxR. [0073] Martello et al., reported that A549 taxane-resistant cell lines required low concentrations of paclitaxel to restore their normal cellular function along with microtubule dynamicity and this might be related to the overexpression of a specific ^III-tubulin isotype. In contrast, the growth of A549/TxR cells did not depend on the continued presence of paclitaxel in the culture media. The resistance mechanism in A549/TxR cell lines is believed to be a higher expression of P-gp. Others suggested that the most likely mechanism of tubulin resistance, caused by efflux of taxanes from cancer cells, is the overexpression of various ABC transporters. Among these transporters, P-gp mediated drug resistance is a contributing factor that limits paclitaxel therapy. Using western blot, the P-gp protein expression in A549 cells was analyzed. The results indicated that resistant cells had a significantly higher expression of P-gp compared with sensitive cells, which is believed to be the reason for paclitaxel ineffectiveness in taxane-resistant cells. Rh123, a well-known tracer dye for P-gp, was added either alone or co-incubated with other drugs. The results indicated that accumulation of Rh-123 in parenteral A549 cells was much higher compared with taxane-resistant cells, which indicated the presence of P-gp in A549/TxR cells. Incubation with Compound 17ya did not affect Rho-123 uptake, suggesting compound 17ya was not a substrate for P-gp. [0074] The most common mechanism of MTAs associated drug resistance is the overexpression of various membrane-bound efflux proteins such as P-gp. P-gp expression was studied in the taxane-resistant A549 cells. Western blot analysis indicated that P-gp protein was highly expressed in the taxane-resistant cell line. Results from flow cytometry confirmed this observation and found much lower accumulation of rhodamine-123 (Rh- 123), a P-gp specific substrate, in the taxane-resistant cells because of the higher activity of efflux transporter that pumped out rhodamine-123 from A549/TxR cells as illustrated in Figure 5A. When co-incubated together, verapamil blocked the efflux pump causing the concentration of Rh123 to become higher in resistant cells. Figure 5B illustrates 76.7% of Rh123 positive cells compared with 3.18% cells in the control. Co-incubation with verapamil and Rh-123 showed slight increment of Rh-123 uptake in sensitive cells suggesting very low presence of P-gp in parenteral cell lines. As shown in figures 5C and 5D, Compound 17ya had no influence on the Rh-123 uptake and thus it was not considered as P-gp substrate. [0075] Compound 17ya interfered in microtubule polymerization via the colchicine binding site. A549 lung cancer cell lines were used to evaluate the interaction between microtubules and Compound 17ya as compared to two known positive controls: paclitaxel (microtubules stabilizer) and colchicine (microtubules destabilizer). The tubulin inhibitors that target colchicine binding site may exert their cytotoxicity through inhibiting microtubule polymerization. Our immunofluorescence study revealed that the cells treated with Compound 17ya enhanced the soluble tubulin accompanied with depolymerized and fragmented microtubules. The colchicine treated cells demonstrated disturbed microtubule assembly, whereas, paclitaxel treated cells caused ring-like concentrated microtubule bundling around the cell nuclei suggesting stabilization of microtubule dynamics. The control cells showed the regular morphology of typical microtubule network distributed evenly throughout the cell cytoplasm in organized manner. [0076] In the resistant cell line, both paclitaxel and colchicine treated groups demonstrated fine-tuned microtubule networks along with regular cytokinesis as compared to the control group. The results demonstrated that neither paclitaxel nor colchicine had any pharmacological effect on A549/TxR cells. In contrast, Compound 17ya caused disruption of microtubule networks and increased the fragmentation. Compound 17ya increased the depolymerized and soluble fraction of tubulin protein in sensitive and resistant A549 cell lines, indicating that compound 17ya was also effective in A549/TxR cells. Thus, Compound 17ya can be used as a cytotoxic chemotherapeutic against taxane resistant lung cancer. [0077] Compound 17ya promoted cell cycle arrest through G2/M phase in A549 and A549/TxR cells. Compound 17ya was tested to determine its effect on cell cycle arrest in lung cancer using a flow cytometry experiment with propidium iodide (PI) staining. Higher concentrations of paclitaxel therapy blocked the G2/M phase in the cell cycle, whereas low concentrations appear to yield a subG1 fraction. Similar results were obtained when 100 nM paclitaxel was incubated for 24 hours in A549 cells. In contrast, treatment with Compound 17ya led to a higher population of cells exhibiting G2/M phase arrest compared to both paclitaxel and colchicine treated groups. The results are illustrated in Figures 6A and 6C. All three tubulin inhibitors (paclitaxel 35.44 ± 6.06%, colchicine 37.77 ± 6.39% and Compound 17ya 47.36 ± 9.53%) exhibited higher G2/M phase arrest compared with untreated cells (7.70 ± 3.85%). Compound 17ya behaved similarly with A549/TxR cell lines, whereas, treatment with paclitaxel failed to trigger G2/M phase arrest as illustrated in Figures 6B and 6D. Colchicine therapy did not yield significant G2/M phase arrest in resistant cells. A549 cells underwent apoptosis induction during treatment with Compound 17ya, paclitaxel, and colchicine. Control cells from parenteral A549 exhibited only 4.44% late stage apoptotic population (both annexin V and PI positive cells). In contrast, treatment with Compound 17ya, paclitaxel, and colchicine showed 12.1%, 7.81%, and 10.9% apoptotic events, respectively. The results are illustrated in Figure 6E. [0078] The antitumor efficacy of Compound 17ya was studied using an A549 tumor xenograft model. Compound 17ya at doses of 7.5 mg/kg and 12.5 mg/kg demonstrated significant dose-dependent anti-tumor efficacy as compared with the control, and illustrated in Figures 7A-7C. Compound 17ya at an oral dosage of 12.5 mg/kg had comparable effect with the paclitaxel treated group when studying tumor volume and tumor weight. The body weight of mice from different treatment groups indicated that none of the tested drugs were toxic at the administered dose and frequency. Compound 17ya exhibited strong tumor suppression in the resistant A549/TxR xenograft model as illustrated in Figures 7D-7F. Treatment with Compound 17ya at oral doses of 7.5 mg/kg and 12.5 mg/kg yielded tumor inhibition of 69% and 77.74%, respectively (p = 0.0008 for 7.5 mg/kg and p = 0.0001 for 12.5 mg/kg). In combination chemotherapy, cisplatin was included as a positive control group, which yielded 70.1% tumor inhibition in lung cancer. The greatest tumor reduction was observed by a combination therapy of 12.5 mg/kg of oral Compound 17ya and 5 mg/kg of intra-peritoneal cisplatin. The combination group demonstrated a slight reduction in mice body weight that indicated cisplatin’s induced toxicity to mice, a similar body weight loss was observed in the cisplatin control group. In the A549/TxR xenograft model, paclitaxel displayed negligible tumor inhibition compared to the control group indicating that paclitaxel therapy was highly ineffective in the taxane-resistant tumor model. [0079] Immunofluorescence studies of the microtubule showed abnormal mitotic figures in drug treated groups. Paclitaxel treated A549 cells displayed microtubule bundling phenotypes, typical signature of microtubule stabilizing agents. Both Compound 17ya and colchicine showed abnormal microtubule organization or depolarization. In A549/TxR resistant cell lines, microtubules from control, paclitaxel, and colchicine treated cells exhibited regular shape with evenly distributed filaments around the cytoplasm and cytokinesis was visible in all three groups. In contrast, cytokinesis was absent in the group treated with Compound 17ya, where proliferation of tumor cells (A549/TxR) was stopped. In parenteral A549 cells, all treatment groups induced G2/M cell cycle arrest; however, only Compound 17ya showed G2/M phase arrest in resistant cell lines. [0080] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention. EXAMPLES [0081] Cell culture and reagents [0082] Human lung cancer cell lines A549 (NSCLC), HCC827 (EGFR mutated epithelial adenocarcinoma), H460 (P53 positive epithelial large cell carcinoma), and H1299 (P53 negative NSCLC) were obtained from American Type Culture Collection (ATCC, Manassas, VA) and cultured in RPMI 1640 medium (Gibco, Carlsbad, CA) containing mixture of 10% fetal bovine serum (FBS, Atlanta Biologicals, Lawrenceville, GA) and 1% antibiotic/antimycotic solution (Sigma-Aldrich, St. Louis, MO). The cells were maintained to 80–90% confluency at 37°C temperature with 5% CO2 in a humidified atmosphere. Paclitaxel-resistant variant of NSCLC A549/TxR cells was derived by the continuous treatment with paclitaxel in nanomolar range (2-200 nM). Paclitaxel treatment was gradually increased from very low concentration and continued for 3-5 days in A549 parenteral cell lines. Meanwhile, the cells were allowed to recover by replacing with drug free culture medium. A549/TxR subline was maintained with the same media containing paclitaxel and shifted with drug-free media a week before actual experiment. [0083] Compound 17ya was synthesized and characterized according to Chen et al., “Discovery of Novel 2-Aryl-4-benzoyl-imidazole (ABI-III) Analogues Targeting tubulin Polymerization as Antiproliferative Agents,” J. Med Chem., 2012, 55, 7285-7289, hereby incorporated by reference. For in-vitro studies, Compound 17ya, paclitaxel or colchicine were prepared in DMSO (ATCC) at a stock concentration of 20 mM and stored in -20 °C in a refrigerator. Prior to experiments, stocks were diluted with the proper culture medium and the final concentration DMSO in drug solution was maintained below 1%. [0084] Cytotoxicity assay [0085] Depending on their growth rate, cancer cell lines were seeded at a concentration of 2.5-5 x10 ³ cells per well in 96-well plate. The next day, the culture medium was replaced with fresh medium containing the test compounds at different concentrations in six to eight replicates. After 72 h of incubation, 20 µL of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] reagent (Promega, Madison, WI) was added to the each well in dark and incubated at 37 °C for 1-3 h depending on the cell type. Absorbance was recorded at 490 nm using a microplate reader (BioTek Instruments Inc., Winooski, VT). The half maximal inhibitory concentration (IC50) values were calculated by GraphPad Prism software (San Diego, CA). [0086] Clonogenic survival assay [0087] In case of clonogenic assay, A549 or A549/TxR cells were seeded in 6-well plates at a very low concentration (500 cells/well). Cells were allowed to attach overnight at 37 °C cells and then treated with paclitaxel, colchicine, or Compound 17ya at different concentrations (0 nM, 4 nM and 16 nM) and incubated for 10 days. Colonies were then fixed with 10% formalin solution for 10-20 min and stained with 0.1% (w/v) crystal violet for 30 min. The excess dye was removed and washed with tap water. The plates were air- dried and the images were taken with Evos Fl imaging system (Life Technologies, Carlsbad, CA). [0088] Wound healing and invasion assay [0089] Sensitive A549 and resistant A549/TxR cells were seeded into the 12-well plates at a cell density of 1 x10 ⁵ /well and incubated overnight. To create uniform identical scratches, a 200 ^L pipet tip was used to make a straight line through the attached cells. Cellular debris was removed with PBS several times. The wells were replaced with fresh medium containing 25 nM single concentration of Compound 17ya, paclitaxel, or colchicine. Control cells remained in a drug-free medium. Photographs were taken at 36 h after drug incubation. Cell invasion assay was done in 24-well Matrigel Invasion Chambers (Corning, Biocoat) according to the manufacturer’s protocol. The cells were treated with different test compounds and incubated for 48 h. Invaded cells in lower chambers were fixed with ice- cold methanol, stained with crystal violet solution, and captured by a microscope. [0090] Immunofluorescence staining [0091] Sub-confluent A549 cells grown overnight on glass coverslips in six-well plates were treated with a concentration of 100 nM of paclitaxel, colchicine or Compound 17ya for 24 h. After washing with PBS, the cells were fixed with 4% paraformaldehyde (PFA) and permeabilized with 0.1% of triton X-100 in PBS solution. Microtubules were stained with anti ^-tubulin antibody (Thermo Scientific, Rockford, IL) overnight at 4 °C, followed by incubation with Alexa Fluor 647 goat anti-mouse IgG (Molecular Probes, Eugene, OR) at room temperature for 1h. The coverslips were washed three times with PBS and mounted on a glass slide with DAPI containing Vectashield antifade mounting media (Vector Lab., Burlingame, CA). The photographs were acquired with a Keyence BZ-X700 fluorescence microscope (Osaka, Japan). [0092] Cell cycle and apoptosis analysis [0093] In order to determine the effects of Compound 17ya on cell cycle distributions, A549 lung cancer cells were seeded into a 6-well plate and incubated with 50 nM concentration of drug solution for 24 hours. Cells were harvested with trypsin and fixed with ice-cold ethanol (70%) overnight. Afterwards, cells were resuspended with 100 µg/mL RNase A (Sigma- Aldrich, St. Louis MO) and the DNA stained with 50 µg/mL propidium iodide (PI) in PBS solution under dark conditions. In the case of an apoptosis assay, the live cells were treated with Annexin V-FITC solution according to the manufacturer instructions (Apoptosis detection kit, BD Biosciences, San Jose, CA). The data acquisition was done by Bio-Rad ZE5 flow cytometer (Bio-Rad, Hercules, CA) and the analysis was performed by FlowJo v10.3. [0094] Western blot [0095] Cell lysates of A549 or A549/TxR cells were prepared with ice-cold RIPA buffer containing protease inhibitor cocktails in standard procedure. The total protein from whole cell lysates was determined by BCA methods as per manufacturer instructions. Equal amounts of protein were resolved on 10% SDS-PAGE gel electrophoresis and transferred onto PVDF membrane. Following protein transfer, the membrane was blocked with 5% skim milk in TBST and probed with primary antibody P-gp (Invitrogen) overnight followed by the appropriate secondary antibody conjugated with horseradish peroxide. Images were developed by chemiluminescence method using ChemiDoc-It2 Imaging System (Bio-Rad, Hercules, CA). [0096] Intracellular Rh123 fluorescence assay [0097] Rhodamine-123 (Rh-123) accumulation in A549 or A549/TxR cells was measured by flow cytometric analysis (FACS) according to Bai et al., BZML, “A novel colchicine binding site inhibitor, overcomes multidrug resistance in A549/Taxol cells by inhibiting P- gp function and inducing mitotic catastrophe,” Cancer Lett., 2017, 402, 81-92. The cells were seeded on a 6-well plate treated with 10 mM Rh-123 and co-incubated with verapamil as a positive control or Compound 17ya for 24 h. After removing unbound dye, cells were re-suspended under dark and immediately analyzed by FACS. [0098] In vivo xenograft model [0099] All Animal experiments followed the guidelines from the National Institute of Health and the protocol approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Tennessee Health Science Center (UTHSC, Memphis, TN). Female nude mice (6–8 weeks old) were purchased from Envigo and maintained under controlled environmental conditions in the animal facility. A549 human lung cancers were suspended in medium and diluted with Matrigel immediately before the injection. 8 × 10 ⁶ A549 cells in 100 ^L were inoculated in the right flank of each mouse. Drug treatment was initiated when the tumor reached around 100 mm ³ . Tumor volume was measured using a caliper and calculated as a × b ² × 0.5, where a and b represented the larger and smaller diameters, respectively. Paclitaxel was dissolved in ethanol and diluted in a 1:1:18 ratio of ethanol:PEG300:PBS solution. Whereas, Compound 17ya was dissolved into PEG300 and diluted into distilled water in a ratio of 3:7. All drug solutions were diluted from the stock solution prior to administration to mice. A total of four groups were used in this study, (i) vehicle treatment; (ii) paclitaxel intraperitoneal (ip) injection of 12.5 mg/kg 3 times per week (3x/wk); (iii) Compound 17ya orally (po) administered 7.5 mg/kg 5 days in a week; and (iv) Compound 17ya (po) 12.5 mg/kg 5 days in a week. [00100] For the paclitaxel resistant A549/TxR model, the tumor inoculation and study procedure remained the same as above. However, two additional groups were included in this experiment; (1) cisplatin 5 mg/kg ip single dose in a week, and (2) the combination of cisplatin and Compound 17ya at a dose of 12.5 mg/kg po. Cisplatin solution was prepared in a warm normal saline solution. [00101] The experiment studied the antitumor efficacy of Compound 17ya in A549 and A549/TxR animal models. Athymic nude mice received 7.5 mg/kg or 12.5 mg/kg oral dose (po) of Compound 17ya every five days in a week and 12.5 mg/kg paclitaxel intraperitoneal (ip) injection for three alternate days in a week. As shown in Figure 7A, A549 xenografted mice showed significant inhibition of tumor growth in all treated groups. Figure 7B results indicated that there was no significant change in mice body weight during the treatment. In Figure 7C, the tumor weight was significantly lower than control. The xenograft study showed A549/TxR resistant tumor volume after treatment with various treatment groups where cisplatin was injected at a dose of 5 mg/kg ip once in a week and the combination group received 12.5 mg/kg po of Compound 17ya and 5 mg/kg ip of cisplatin. See Figure 7D. Only cisplatin therapy alone or in combination with Compound 17ya showed a slight reduction in mice body weight as illustrated in Figure 7E. Figure 7G reports the quantitative analysis of tumor weight from the differently treated groups. The data was represented as the mean±SEM(n=5-7) and the statistical analysis was performed by Dunnett multiple comparison test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 versus control or indicated. [00102] Immunohistochemistry [00103] The excised tumor tissue and other major organ were collected in 10% formalin solution and embedded in paraffin. Serial sections were obtained and stained with hematoxylin and eosin (H&E) and immunohistochemistry. IHC staining was performed with rabbit anti-cleaved caspase 3 antibody (Cell Signaling Technology Inc., Danvers, MA) and rabbit anti-CD31 (Cell Signaling Technology Inc., Danvers, MA) following ABC-DAB methods. Antigen retrieval was performed with H-3300 antigen unmasking solution (Vector Laboratories, Burlingame, CA). Slides were imaged and analyzed with a Keyence BZ-X700 microscope and BZ-X analyzer software (Keyence, Osaka, Japan). [00104] Statistical Analysis [00105] All data were analyzed using GraphPad Prism 7.0 (GraphPad Software, Inc., San Diego, CA). Data were provided as the mean ± SEM unless otherwise indicated. The statistical significance (P < 0.05) was calculated by one-way ANOVA and Student’s t-test.