Computer assisted design of second-generation colchicine derivatives

Interdisciplinary Sciences, Computational Life Sciences
J Torin HuzilJack A Tuszynski

Abstract

Cytoskeletal proteins, such as tubulin, are a primary target for many successful anti-cancer drugs. The expression of several beta-tubulin isotypes in normal and cancerous cells provides a platform upon which to construct chemotherapeutic agents capable of differentiating between them. To test this hypothesis, we have previously designed several colchicine derivatives and computationally probed them for affinity to the beta-tubulin isotypes. Subsequent synthesis and cytotoxicity assays produced a small set of promising compounds exhibiting IC(50) values approximately 30 fold lower than values previously reported for colchicine. Here we describe the creation and testing of these first-generation colchicine derivatives and discuss the subsequent design and preliminary computational screening of a novel set of second-generation derivatives using the most promising first-generation derivatives as scaffolds.

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Feb 28, 2006·Nanotechnology·J Torin HuzilJack Tuszynski

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Citations

Oct 9, 2014·BioMed Research International·Md Ashrafuzzaman
Sep 26, 2012·Chemical Biology & Drug Design·Mohammad AshrafuzzamanJack A Tuszynski
Feb 18, 2014·Biochemical and Biophysical Research Communications·Md AshrafuzzamanJ A Tuszynski
Oct 13, 2011·ChemMedChem·Alberto MassarottiAndrea Brancale
Aug 1, 2019·Current Drug Targets·Jobin JoseBijo Mathew
May 21, 2020·Journal of Medicinal Chemistry·Iuliia A GrachevaAlexey Yu Fedorov

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