Toward a rational design of selective multi-trypanosomatid inhibitors: a computational docking study.
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.
Espinoza-Fonseca
L Michel
LM
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Trujillo-Ferrara
José G
JG
D000818:Animals; D015195:Drug Design; D004748:Entamoeba histolytica / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014961:X-Ray Diffraction
D014344:Trypanocidal Agents