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

Bioorg Med Chem Lett. 2015 May 1;25(9):1982-5. doi: 10.1016/j.bmcl.2015.03.019.

Sangram S Kale ¹, Ganesh S Jedhe ¹, Sachin N Meshram ², Manas K Santra ², Ernest Hamel ³, Gangadhar J Sanjayan ⁴

Affiliations

1 Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India.
2 National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune 411 007, Maharashtra, India.
3 Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States.
4 Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India. Electronic address: [email protected].

PMID: 25817588 DOI: 10.1016/j.bmcl.2015.03.019

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 μM IC50 values in both assays.

Keywords

Anticancer; Colchicine; Nocodazole; Tubulin binding.

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