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Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity.

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 compounds 2, 3 and 4 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 Compounds 1 and 4 showed ?M IC50 values in both assays.

SUBMITTER: Kale SS

PROVIDER: S-EPMC4416488 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity.

Kale Sangram S SS Jedhe Ganesh S GS Meshram Sachin N SN Santra Manas K MK Hamel Ernest E Sanjayan Gangadhar J GJ

Bioorganic & medicinal chemistry letters 20150314 9

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 compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubul ...[more]

PMID: 25817588

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