Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs

Bioorganic & Medicinal Chemistry Letters
Michael CifuentesMark E Janik

Abstract

A series of modified colchicine and isocolchicine analogs (C-7 substituent) were synthesized and evaluated in vitro against a PC3 cancer cell line and for inhibition of microtubule polymerization. The colchicine analogs all displayed strong inhibition of tubulin polymerization, while compounds 6 and 20 also possessed an increased cytotoxic activity as compared to colchicine. More importantly, isocolchicine analogs 7, 15, and 17 showed inhibition of microtubule polymerization with IC(50) values ranging from 58 to 68muM. In addition, 7 displayed strong cytotoxic activity with an IC(50)=93nM which was more potent than colchicine analog 12.

References

Jan 1, 1982·Methods in Enzymology·R C Williams, J C Lee
May 1, 1981·Journal of Medicinal Chemistry·F R QuinnJ A Beisler
Nov 11, 1999·Medicinal Research Reviews·K H Lee

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Citations

Oct 19, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mengqi DongBing Yan
Apr 22, 2015·Organic & Biomolecular Chemistry·Baljinder SinghRam A Vishwakarma
Sep 27, 2018·Medicinal Chemistry·Apilak WorachartcheewanVirapong Prachayasittikul

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