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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

hemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitor

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Author(s):
Medeiros, Alex R. [1] ; Ferreira, Leonardo L. G. [1] ; de Souza, Mariana L. [1] ; de Oliveira Rezende Junior, Celso [2] ; Espinoza-Chavez, Rocio Marisol [2] ; Dias, Luiz Carlos [2] ; Andricopulo, Adriano D. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Ctr Pesquisa & Inovacao Biodivers & Farmacos, Lab Quim Med & Computac, Av Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil
[2] Univ Estadual Campinas, Inst Quim, BR-13084971 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: BIOMOLECULES; v. 11, n. 4 APR 2021.
Web of Science Citations: 0
Abstract

Natural products based on imidazole scaffolds have inspired the discovery of a wide variety of bioactive compounds. Herein, a series of imidazoles that act as competitive and potent cruzain inhibitors was investigated using a combination of ligand- and structure-based drug design strategies. Quantitative structure-activity relationships (QSARs) were generated along with the investigation of enzyme-inhibitor molecular interactions. Predictive hologram QSAR (HQSAR, r(pred)(2) = 0.80) and AutoQSAR (q(2) = 0.90) models were built, and key structural properties that underpin cruzain inhibition were identified. Moreover, comparative molecular field analysis (CoMFA, r(pred)(2) = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r(pred)(2) = 0.73) revealed 3D molecular features that strongly affect the activity of the inhibitors. These findings were examined along with molecular docking studies and were highly compatible with the intermolecular contacts that take place between cruzain and the inhibitors. The results gathered herein revealed the main factors that determine the activity of the imidazoles studied and provide novel knowledge for the design of improved cruzain inhibitors. (AU)

FAPESP's process: 13/25658-9 - Design and Development of Drug Candidates for Chagas Disease
Grantee:Leonardo Luiz Gomes Ferreira
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 18/14268-9 - Converting natural product leads into structure- and ligand-based drug discovery campaigns against Leishmaniasis and Chagas' Disease
Grantee:Adriano Defini Andricopulo
Support Opportunities: Research Projects - Thematic Grants