Neglected Tropical Diseases: A Chemoinformatics Approach for the Use of Biodiversity in Anti-Trypanosomatid Drug Discovery

Author(s)

Valli, Marilia ; Doering, Thiago H. ; Marx, Edgard ; Ferreira, Leonardo L. G. ; Medina-Franco, Jose L. ; Andricopulo, Adriano D.

• Document type: Journal article
• Source: BIOMOLECULES; v. 14, n. 8, p. 19-pg., 2024-08-01.

Abstract

The development of new treatments for neglected tropical diseases (NTDs) remains a major challenge in the 21st century. In most cases, the available drugs are obsolete and have limitations in terms of efficacy and safety. The situation becomes even more complex when considering the low number of new chemical entities (NCEs) currently in use in advanced clinical trials for most of these diseases. Natural products (NPs) are valuable sources of hits and lead compounds with privileged scaffolds for the discovery of new bioactive molecules. Considering the relevance of biodiversity for drug discovery, a chemoinformatics analysis was conducted on a compound dataset of NPs with anti-trypanosomatid activity reported in 497 research articles from 2019 to 2024. Structures corresponding to different metabolic classes were identified, including terpenoids, benzoic acids, benzenoids, steroids, alkaloids, phenylpropanoids, peptides, flavonoids, polyketides, lignans, cytochalasins, and naphthoquinones. This unique collection of NPs occupies regions of the chemical space with drug-like properties that are relevant to anti-trypanosomatid drug discovery. The gathered information greatly enhanced our understanding of biologically relevant chemical classes, structural features, and physicochemical properties. These results can be useful in guiding future medicinal chemistry efforts for the development of NP-inspired NCEs to treat NTDs caused by trypanosomatid parasites. (AU)

• FAPESP's process: 20/11967-3 - Sustainable use of Brazilian biodiversity: using Linked Data for natural product discovery
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• 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: 22/08333-8 - Accelerating natural product discovery
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: Regular Research Grants
• 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