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

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 8; p. 1033
• Main Authors: Valli, Marilia, Döring, Thiago H, Marx, Edgard, Ferreira, Leonardo L G, Medina-Franco, José L, Andricopulo, Adriano D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-08-2024; MDPI
• Subjects: Animals; Benzoic acid; Biodiversity; Bioflavonoids; Biological diversity; Biological Products - chemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Care and treatment; chagas disease; Cheminformatics - methods; Clinical trials; COVID-19; Diseases; Drug development; Drug discovery; Drug Discovery - methods; Drugs; Flavones; Flavonoids; human African trypanosomiasis; Humans; Lead compounds; leishmaniasis; Natural products; Neglected Diseases - drug therapy; neglected tropical diseases; Parasites; Phenylpropanoids; Physicochemical properties; Polyketides; Protozoa; R&D; Research & development; Steroid hormones; Tropical diseases; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanocidal Agents - therapeutic use; Trypanosoma - drug effects; New York; United States > US; Switzerland; natural products; human African trypanosomiasis; chagas disease; neglected tropical diseases; drug discovery; leishmaniasis
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14081033

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.