Design, synthesis, and biological evaluation of stable colchicine binding site tubulin inhibitors as potential anticancer agents

Journal of Medicinal Chemistry

Volumn 57, Issue 17, 2014, Pages 7355-7366

  Lu, Yan ^a   Chen, Jianjun ^a   Wang, Jin ^a   Li, Chien Ming ^b   Ahn, Sunjoo ^b   Barrett, Christina M ^b   Dalton, James T ^b   Li, Wei ^a   Miller, Duane D ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b GTx Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(4 HYDROXY 3,5 DIMETHOXYPHENYL)(2 PHENYLTHIAZOL 4 YL)METHANONE; 2 (1H INDOL 5 YL) 4 (3,4,5 TRIMETHOXYPHENYL) 1H BENZO[D]IMIDAZOLE; 2 (1H INDOL 5 YL) 4 (3,4,5 TRIMETHOXYPHENYL) 1H IMIDAZO[4,5 C]PYRIDINE; 2 (1H INDOL 5 YLAMINO) N METHOXY N METHYLTHIAZOLE 4 CARBOXAMIDE; 2 [2 [2,6 DIMETHOXY 4 (2 PHENYLTHIAZOLE 4 CARBONYL)PHENOXY]ETHYL]ISOINDOLINE 1,3 DIONE; 2,6 DIMETHOXY 4 (2 PHENYLTHIAZOLE 4 CARBONYL)PHENYL 2 CHLOROACETATE; 2,6 DIMETHOXY 4 (2 PHENYLTHIAZOLE 4 CARBONYL)PHENYL 2,2,2 TRIFLUOROACETATE; 3 [4 (3,4,5 TRIMETHOXYPHENYL) 1H BENZO[D]IMIDAZOL 2 YL] 1H INDAZOLE; 3,4,5 TRIMETHOXY N PHENYL N [1 (PHENYLSULFONYL) 1H IMIDAZOL 2 YL]BENZAMIDE; ANTINEOPLASTIC AGENT; BENZIMIDAZOLE DERIVATIVE; COLCHICINE; IMIDAZO[4,5 C]PYRIDINE DERIVATIVE; N (1H IMIDAZOL 2 YL) 3,4,5 TRIMETHOXY N PHENYLBENZAMIDE; N (2,2 DIETHOXYETHYL)CARBODIIMIDE; N PHENYL 1 TRITYL 1H IMIDAZOL 2 AMINE; N PHENYL 1H IMIDAZOL 2 AMINE; N PHENYL 4 TRITYL 1H IMIDAZOL 2 AMINE; N [(1H INDOL 5 YL)CARBAMOTHIOYL]BENZAMIDE; UNCLASSIFIED DRUG; [2 (PHENYLAMINO) 1H IMIDAZOL 4 YL](3,4,5 TRIMETHOXYPHENYL)METHANONE; [2 [(1H INDOL 5 YL)AMINO]THIAZOL 4 YL](3,4,5 TRIMETHOXYPHENYL)METHANONE; [3,5 DIMETHOXY 4 (METHOXYMETHOXY)PHENYL](2 PHENYLTHIAZOL 4 YL)METHANONE; [4 (2 AMINOETHYL) 3,5 DIMETHOXYPHENYL](2 PHENYLTHIAZOL 4 YL)METHANONE; [4 (BENZYLOXY) 3,5 DIMETHOXYPHENYL](2 PHENYLTHIAZOL 4 YL)METHANONE; PROTEIN BINDING; TUBULIN MODULATOR;

ALKYLATION; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; COVALENT BOND; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG IDENTIFICATION; DRUG SCREENING; DRUG SYNTHESIS; HYDROGEN BOND; IN VITRO STUDY; LIVER MICROSOME; MELANOMA CELL LINE; MICROTUBULE ASSEMBLY; MOLECULAR MODEL; PROSTATE CANCER CELL LINE; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION; BINDING SITE; CELL PROLIFERATION; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; HUMAN; METABOLISM; PROTEIN TERTIARY STRUCTURE; SYNTHESIS; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE, TUMOR; CELL PROLIFERATION; COLCHICINE; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN MODULATORS;

EID: 84921448698     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500764v     Document Type: Article

References (24)

1. Jordan, M. A.; Wilson, L. Microtubules as a target for anticancer drugs Nat. Rev. Cancer 2004, 4 (4) 253-265
2. Lu, Y.; Chen, J.; Xiao, M.; Li, W.; Miller, D. D. An overview of tubulin inhibitors that interact with the colchicine binding site Pharm. Res. 2012, 29 (11) 2943-2971
3. Nam, N. H. Combretastatin A-4 analogues as antimitotic antitumor agents Curr. Med. Chem. 2003, 10 (17) 1697-1722
4. Pettit, G. R.; Toki, B.; Herald, D. L.; Verdier-Pinard, P.; Boyd, M. R.; Hamel, E.; Pettit, R. K. Antineoplastic agents. 379. Synthesis of phenstatin phosphate J. Med. Chem. 1998, 41 (10) 1688-1695
5. Kuo, C. C.; Hsieh, H. P.; Pan, W. Y.; Chen, C. P.; Liou, J. P.; Lee, S. J.; Chang, Y. L.; Chen, L. T.; Chen, C. T.; Chang, J. Y. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo Cancer Res. 2004, 64 (13) 4621-4628
6. Sriram, M.; Hall, J. J.; Grohmann, N. C.; Strecker, T. E.; Wootton, T.; Franken, A.; Trawick, M. L.; Pinney, K. G. Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy Bioorg. Med. Chem. 2008, 16 (17) 8161-8171
7. Liu, X.; Go, M. L. Antiproliferative properties of piperidinylchalcones Bioorg. Med. Chem. 2006, 14 (1) 153-163
8. Burns, R. G. Analysis of the colchicine-binding site of beta-tubulin FEBS Lett. 1992, 297 (3) 205-208
9. Alvarez, C.; Alvarez, R.; Corchete, P.; Perez-Melero, C.; Pelaez, R.; Medarde, M. Exploring the effect of 2,3,4-trimethoxy-phenyl moiety as a component of indolephenstatins Eur. J. Med. Chem. 2010, 45 (2) 588-97
10. Brancale, A.; Silvestri, R. Indole, a core nucleus for potent inhibitors of tubulin polymerization Med. Res. Rev. 2007, 27 (2) 209-38
11. Ray, K.; Bhattacharyya, B.; Biswas, B. B. Role of B-ring of colchicine in its binding to tubulin J. Biol. Chem. 1981, 256 (12) 6241-6244
12. Lu, Y.; Li, C. M.; Wang, Z.; Ross, C. R., II; Chen, J.; Dalton, J. T.; Li, W.; Miller, D. D. Discovery of 4-substituted methoxybenzoyl-aryl-thiazole as novel anticancer agents: synthesis, biological evaluation, and structure-activity relationships J. Med. Chem. 2009, 52 (6) 1701-1711
13. Chen, J.; Li, C. M.; Wang, J.; Ahn, S.; Wang, Z.; Lu, Y.; Dalton, J. T.; Miller, D. D.; Li, W. Synthesis and antiproliferative activity of novel 2-aryl-4-benzoyl-imidazole derivatives targeting tubulin polymerization Bioorg. Med. Chem. 2011, 19 (16) 4782-4795
14. Li, C. M.; Chen, J.; Lu, Y.; Narayanan, R.; Parke, D. N.; Li, W.; Ahn, S.; Miller, D. D.; Dalton, J. T. Pharmacokinetic optimization of 4-substituted methoxybenzoyl-aryl-thiazole and 2-aryl-4-benzoyl-imidazole for improving oral bioavailability Drug Metab. Dispos. 2011, 39 (10) 1833-1839
15. Wang, Z.; Chen, J.; Wang, J.; Ahn, S.; Li, C. M.; Lu, Y.; Loveless, V. S.; Dalton, J. T.; Miller, D. D.; Li, W. Novel tubulin polymerization inhibitors overcome multidrug resistance and reduce melanoma lung metastasis Pharm. Res. 2012, 29 (11) 3040-3052
16. Li, C. M.; Wang, Z.; Lu, Y.; Ahn, S.; Narayanan, R.; Kearbey, J. D.; Parke, D. N.; Li, W.; Miller, D. D.; Dalton, J. T. Biological activity of 4-substituted methoxybenzoyl-aryl-thiazole: an active microtubule inhibitor Cancer Res. 2011, 71 (1) 216-224
17. Li, C. M.; Lu, Y.; Narayanan, R.; Miller, D. D.; Dalton, J. T. Drug metabolism and pharmacokinetics of 4-substituted methoxybenzoyl-aryl-thiazoles Drug Metab. Dispos. 2010, 38 (11) 2032-2039
18. Bai, R.; Covell, D. G.; Pei, X. F.; Ewell, J. B.; Nguyen, N. Y.; Brossi, A.; Hamel, E. Mapping the binding site of colchicinoids on beta-tubulin. 2-Chloroacetyl-2-demethylthiocolchicine covalently reacts predominantly with cysteine 239 and secondarily with cysteine 354 J. Biol. Chem. 2000, 275 (51) 40443-40452
19. Bai, R. L.; Lin, C. M.; Nguyen, N. Y.; Liu, T. Y.; Hamel, E. Identification of the cysteine residue of beta-tubulin alkylated by the antimitotic agent 2,4-dichlorobenzyl thiocyanate, facilitated by separation of the protein subunits of tubulin by hydrophobic column chromatography Biochemistry 1989, 28 (13) 5606-5612
20. Shan, B.; Medina, J. C.; Santha, E.; Frankmoelle, W. P.; Chou, T. C.; Learned, R. M.; Narbut, M. R.; Stott, D.; Wu, P.; Jaen, J. C.; Rosen, T.; Timmermans, P. B.; Beckmann, H. Selective, covalent modification of beta-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors Proc. Natl. Acad. Sci. U.S.A. 1999, 96 (10) 5686-5691
21. Slominski, A. T.; Kim, T. K.; Li, W.; Yi, A. K.; Postlethwaite, A.; Tuckey, R. C. The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions J. Steroid Biochem. Mol. Biol. 2013, 10.1016/j.jsbmb.2013.10.012
22. Xiao, M.; Ahn, S.; Wang, J.; Chen, J.; Miller, D. D.; Dalton, J. T.; Li, W. Discovery of 4-aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with potent antiproliferative properties J. Med. Chem. 2013, 56 (8) 3318-3329
23. Chen, J.; Ahn, S.; Wang, J.; Lu, Y.; Dalton, J. T.; Miller, D. D.; Li, W. Discovery of novel 2-aryl-4-benzoyl-imidazole (ABI-III) analogues targeting tubulin polymerization as antiproliferative agents J. Med. Chem. 2012, 55 (16) 7285-7289
24. Chen, J.; Wang, J.; Kim, T. K.; Tieu, E. W.; Tang, E. K.; Lin, Z.; Kovacic, D.; Miller, D. D.; Postlethwaite, A.; Tuckey, R. C.; Slominski, A. T.; Li, W. Novel vitamin d analogs as potential therapeutics: metabolism, toxicity profiling, and antiproliferative activity Anticancer Res. 2014, 34 (5) 2153-2163