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Toward a rational design of selective multi-trypanosomatid inhibitors: a computational docking study |
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| Authors: | Espinoza-Fonseca L Michel Trujillo-Ferrara José G |
| Affiliation: | aDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA bEscuela Superior de Medicina del Instituto Politécnico Nacional, Apartado Postal 42-161, C.P. 11340, Mexico City, Mexico cDepartamento de Bioquı´mica, Escuela Superior de Medicina del Instituto Politécnico Nacional, Apartado Postal 42-161, C.P. 11340, Mexico City, Mexico |
| Abstract: | Compound V7, a benzothiazole which was recently found as selective inhibitor of trypanosomal TIMs, was docked into TIMs from Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Plasmodium falciparum, yeast, and human. Structural analyses revealed the importance of the accessibility to the two aromatic clusters located at the dimer’s interface for the selective inhibition of trypanosomal TIMs. Thus, it was found that different accessibilities of the protein interface of TIMs plays an important role in the inhibitory activity of benzothiazoles. These findings will contribute to the rational development and improvement of benzothiazoles to be used as multi-trypanosomatid inhibitors. |
| Keywords: | Computational docking Trypanosomatid inhibitors Trypanosoma cruzi Trypanosoma brucei Triosephosphate isomerase Aromatic clusters |
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