Identification of Selective Tubulin Inhibitors As Potential Anti-Trypanosomal Agents

Document Type

Article

Publication Date

9-1-2012

Publication Title

Bioorganic and Medicinal Chemistry Letters

Abstract

The potency of a series of sulfonamide tubulin inhibitors against the growth of Trypanosoma brucei (T. brucei), as well as human cancer and primary fibroblast cells were evaluated with the aim of determining whether compounds that selectively inhibit parasite proliferation could be identified. Several compounds showed excellent selectivity against T. brucei growth, and have the potential to be used for the treatment of Human African trypanosomiasis. A T. brucei tubulin protein homology model was built based on the crystal structure of the bovine tubulin. The colchicine-binding domain, which is also the binding site of the tested sulfonamide tubulin inhibitors, showed clear differences between the tubulin structures and presumably explained the selectivity of the compounds. © 2012 Elsevier Ltd. All rights reserved.

DOI

10.1016/j.bmcl.2012.07.023

Volume

22

Issue

17

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