91918-57-9Relevant articles and documents
Synthesis and biological evaluation of imidazo[2,1-b][1,3,4]thiadiazole- linked oxindoles as potent tubulin polymerization inhibitors
Kamal, Ahmed,Rao, M. P. Narasimha,Das, Pompi,Swapna,Polepalli, Sowjanya,Nimbarte, Vijaykumar D.,Mullagiri, Kishore,Kovvuri, Jeshma,Jain, Nishant
, p. 1463 - 1475 (2014/07/21)
A series of imidazo[2,1-b][1,3,4]thiadiazole-linked oxindoles composed of an A, B, C and D ring system were synthesized and investigated for anti-proliferative activity in various human cancer cell lines; test compounds were variously substituted at rings C and D. Among them, compounds 7 ((E)-5-fluoro-3-((6-p-tolyl-2-(3,4,5-trimethoxyphenyl)-imidazo[2,1-b][1,3,4] thiadiazol-5-yl)methylene)indolin-2-one), 11 ((E)-3-((6-p-tolyl-2-(3,4,5- trimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)indolin-2-one), and 15 ((E)-6-chloro-3-((6-phenyl-2-(3,4,5-trimethoxyphenyl)imidazo[2,1-b][1,3, 4]thiadiazol-5-yl)methylene)indolin-2-one) exhibited potent anti-proliferative activity. Treatment with these three compounds resulted in accumulation of cells in G2/M phase, inhibition of tubulin assembly, and increased cyclin-B1 protein levels. Compound 7 displayed potent cytotoxicity, with an IC50 range of 1.1-1.6 μM, and inhibited tubulin polymerization with an IC50 value (0.15 μM) lower than that of combretastatin A-4 (1.16 μM). Docking studies reveal that compounds 7 and 11 bind with αAsn101, βThr179, and βCys241 in the colchicine binding site of tubulin. Imidazzling microtubule blockers! A series of imidazo[2,1-b][1,3,4] thiadiazole-linked oxindole conjugates were synthesized and evaluated for anticancer potential. Conjugate 7 displayed promising cytotoxicity, arrested cells at the G2/M phase, and showed potent tubulin polymerization inhibition with an IC50 value of 0.15 μM.
