Jedhe , G.S. and Paul , D. and Gonnade , R.G. and Santra , M.K. and Hamel , E. and Nguyen , T.L. and Sanjayan , G.J. (2013) Correlation of hydrogen-bonding propensity and anticancer profile of tetrazole-tethered combretastatin analogues. Bioorganic & Medicinal Chemistry Letters, 23 (16). 4680-4.. ISSN 013 Aug 15;23(16):4680-4.

Text 17. Dr. Manas S. (Bioorg Med Chem Lett.) Author Copy.pdf - Accepted Version Restricted to Registered users only Download (299Kb) | Request a copy

Abstract

A series of 1,5-disubstituted tetrazole-tethered combretastatin analogues with extended hydrogen-bond donors at the ortho-positions of the aryl A and B rings were developed and evaluated for their antitubulin and antiproliferative activity. We wanted to test whether intramolecular hydrogen-bonding used as a conformational locking element in these analogues would improve their activity. The correlation of crystal structures with the antitubulin and antiproliferative profiles of the modified analogues suggested that hydrogen-bond-mediated conformational control of the A ring is deleterious to the bioactivity. In contrast, although there was no clear evidence that intramolecular hydrogen bonding to the B ring enhanced activity, we found that increased substitution on the B ring had a positive effect on antitubulin and antiproliferative activity. Among the various analogues synthesized, compounds 5d and 5e, having hydrogen-bonding donor groups at the ortho and meta-positions on the 4-methoxy phenyl B ring, are strong inhibitors of tubulin polymerization and antiproliferative agents having IC50 value in micromolar concentrations.

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	22 Apr 2015 08:35
Last Modified:	30 Jun 2015 11:16
URI:	http://nccs.sciencecentral.in/id/eprint/97

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