TY - JOUR
T1 - Toward a rational design of selective multi-trypanosomatid inhibitors
T2 - A computational docking study
AU - Espinoza-Fonseca, L. Michel
AU - Trujillo-Ferrara, José G.
N1 - Funding 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.
PY - 2006/12/15
Y1 - 2006/12/15
N2 - 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.
AB - 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.
KW - Aromatic clusters
KW - Computational docking
KW - Triosephosphate isomerase
KW - Trypanosoma brucei
KW - Trypanosoma cruzi
KW - Trypanosomatid inhibitors
UR - http://www.scopus.com/inward/record.url?scp=33750684639&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2006.09.029
DO - 10.1016/j.bmcl.2006.09.029
M3 - Artículo
C2 - 16997551
SN - 0960-894X
VL - 16
SP - 6288
EP - 6292
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 24
ER -