Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site

Chenxiao Da; Nakul Telang; Kayleigh Hall; Emily Kluball; Peter Barelli; Kara Finzel; Xin Jia; John T Gupton; Susan L Mooberry; Glen E Kellogg

doi:10.1039/C2MD20320K

Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site

Medchemcomm. 2013;4(2):417-421. doi: 10.1039/C2MD20320K.

Authors

Affiliations

¹ Department of Medicinal Chemistry & Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, USA 23298-0540.
² Department of Chemistry, Gottwald Center for the Sciences, University of Richmond, Richmond, Virginia, USA 23173.
³ Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA 78229-3900.

Abstract

The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an appropriately positioned acceptor for Cys241β in the otherwise hydrophobic subpocket A.

Abstract

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