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.
Bibliographical noteFunding Information:
The authors thank the anonymous reviewers for their unbiased criticisms. This work was supported, in part, by grants from CONACYT-SNI and SIP-IPN to J.G.T.F.
- Aromatic clusters
- Computational docking
- Triosephosphate isomerase
- Trypanosoma brucei
- Trypanosoma cruzi
- Trypanosomatid inhibitors