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

Author(s)

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 16, p. 16-pg., 2022-08-01.

Abstract

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)

• FAPESP's process: 19/05967-3 - Understanding the biological function of Natural Products' scaffolds from Databases for the design of active compounds for the treatment of infectious diseases
• Grantee: Marilia Valli
• 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