Molecular modeling and structure-activity relationships for a series of benzimidazole derivatives as cruzain inhibitors

Future Medicinal Chemistry
Ivani PauliAdriano D Andricopulo

Abstract

Chagas disease is endemic in Latin America and no effective treatment is available. Efforts in drug research have focused on several enzymes from Trypanosoma cruzi, among which cruzain is a validated pharmacological target. Chemometric analyses were performed on the data set using the hologram quantitative structure-activity relationship, comparative molecular field analysis and comparative molecular similarity index analysis methods. Docking simulations were executed using the crystallographic structure of cruzain in complex with a benzimidazole inhibitor. The top-scoring enzyme-inhibitor complexes were selected for the development of the 3D quantitative structure-activity relationship (QSAR) models and to assess the inhibitor binding modes and intermolecular interactions. Benzimidazole derivatives as cruzain inhibitors were used in molecular docking and QSAR studies. Significant statistical indicators were obtained, and the best models demonstrated high predictive ability for an external test set (r2pred= 0.65, 0.94 and 0.82 for hologram QSAR, comparative molecular field analysis and comparative molecular similarity index analysis, respectively). Additionally, the graphical information of the chemometric analyses demonstrated...Continue Reading

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Citations

Feb 17, 2018·Anais Da Academia Brasileira De Ciências·Leonardo G FerreiraAdriano D Andricopulo
Nov 1, 2018·Current Medicinal Chemistry·Amit Kumar Halder, M Natália Dias Soeiro Cordeiro
Jul 13, 2019·Current Medicinal Chemistry·Marcus Tullius ScottiLuciana Scotti
Aug 21, 2019·Frontiers in Pharmacology·Ana Catarina Cristovão SilvaMarcelo Zaldini Hernandes
Aug 31, 2019·Future Medicinal Chemistry·Glaécia An PereiraRafaela S Ferreira
Mar 23, 2021·ACS Omega·Jose Guadalupe Rosas-JimenezKarina Martinez-Mayorga
May 1, 2021·Biomolecules·Alex R MedeirosAdriano D Andricopulo
Dec 12, 2018·Journal of Chemical Information and Modeling·Lucianna H SantosRafaela S Ferreira

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Methods Mentioned

BETA
PCA

Software Mentioned

GOLD
HQSAR
Pymol
SYBYL
Tripos
CentOS Linux
ChemScore
CoMFA
CoMSIA

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