Hierarchical Clustering and Target-Independent QSAR for Antileishmanial Oxazole and Oxadiazole Derivatives

Autor(es)

Teles, Henrique R. ; Ferreira, Leonardo L. G. ; Valli, Marilia ; Coelho, Fernando ; Andricopulo, Adriano D.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 16, p. 16-pg., 2022-08-01.

Resumo

Leishmaniasis is a neglected tropical disease that kills more than 20,000 people each year. The chemotherapy available for the treatment of the disease is limited, and novel approaches to discover novel drugs are urgently needed. Herein, 2D- and 4D-quantitative structure-activity relationship (QSAR) models were developed for a series of oxazole and oxadiazole derivatives that are active against Leishmania infantum, the causative agent of visceral leishmaniasis. A clustering strategy based on structural similarity was applied with molecular fingerprints to divide the complete set of compounds into two groups. Hierarchical clustering was followed by the development of 2D- (R-2 = 0.90, R(2)pred = 0.82) and 4D-QSAR models (R-2 = 0.80, R(2)pred = 0.64), which showed improved statistical robustness and predictive ability. (AU)

• Processo FAPESP: 19/05967-3 - Compreensão da função biológica de produtos naturais de Bases de Dados para o planejamento de compostos ativos para o tratamento de doenças infecciosas
• Beneficiário: Marilia Valli
• 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