Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity. Issue 9 (1st May 2015)

• Record Type: Journal Article
• Authors: Kale, Sangram S.; Jedhe, Ganesh S.; Meshram, Sachin N.; Santra, Manas K.; Hamel, Ernest; Sanjayan, Gangadhar J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 9(2015)
• Page Start: 1982
• Page End: 1985
• Publication Date: 2015-05-01
• Subjects: Tubulin binding -- Nocodazole -- Colchicine -- Anticancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.019
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We describe the design, synthesis and SAR profiling of a series of novel combretastatin–nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds2, 3 and4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds1 and4 showed μM IC50 values in both assays.