hemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitor

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: BIOMOLECULES; v. 11, n. 4 APR 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 13/25658-9 - Planejamento e Desenvolvimento de Candidatos a Fármacos para a Doença de Chagas
• Beneficiário: Leonardo Luiz Gomes Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/14268-9 - Descoberta de fármacos baseada na estrutura do receptor e do ligante para a Leishmaniose e a Doença de Chagas a partir de produtos naturais bioativos
• Beneficiário: Adriano Defini Andricopulo
• Modalidade de apoio: Auxílio à Pesquisa - Temático