Identification of selective tubulin inhibitors as potential anti-trypanosomal agents

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Lama, Rati²  Sandhu, Ranjodh¹  Zhong, Bo²  Li, Bibo^1,3  Su, Bin^2,3 

[1] Cleveland State Univ, Dept Biol Geo & Env Sci, Coll Sci & Hlth Profess, Cleveland, OH 44115 USA

[2] Cleveland State Univ, Dept Chem, Coll Sci & Hlth Profess, Cleveland, OH 44115 USA

[3] Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Coll Sci & Hlth Profess, Cleveland, OH 44115 USA

关键词: Trypanosomiasis;    Tubulin inhibitor;    Sulfonamide;    Drug development;   

DOI  :  10.1016/j.bmcl.2012.07.023

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Ltd.

【 授权许可】

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