Toward a rational design of selective multi-trypanosomatid inhibitors: A computational docking study

L. Michel Espinoza-Fonseca; José G. Trujillo-Ferrara

doi:10.1016/j.bmcl.2006.09.029

Toward a rational design of selective multi-trypanosomatid inhibitors: A computational docking study

L. Michel Espinoza-Fonseca, José G. Trujillo-Ferrara

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English (US)
Pages (from-to)	6288-6292
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2006.09.029
State	Published - Dec 15 2006
Externally published	Yes

Bibliographical note

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.

Keywords

Aromatic clusters
Computational docking
Triosephosphate isomerase
Trypanosoma brucei
Trypanosoma cruzi
Trypanosomatid inhibitors

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10.1016/j.bmcl.2006.09.029

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title = "Toward a rational design of selective multi-trypanosomatid inhibitors: A computational docking study",

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 = "Aromatic clusters, Computational docking, Triosephosphate isomerase, Trypanosoma brucei, Trypanosoma cruzi, Trypanosomatid inhibitors",

author = "Espinoza-Fonseca, {L. Michel} and Trujillo-Ferrara, {Jos{\'e} G.}",

note = "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. ",

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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

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Toward a rational design of selective multi-trypanosomatid inhibitors: A computational docking study

Abstract

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Keywords

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