Neglected Tropical Diseases: A Chemoinformatics Approach for the Use of Biodiversity in Anti-Trypanosomatid Drug Discovery
Marilia Valli,
Thiago H. Döring,
Edgard Marx,
Leonardo L. G. Ferreira,
José L. Medina-Franco,
Adriano D. Andricopulo
Affiliations
Marilia Valli
Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n° 1100, Sao Carlos 13563-120, SP, Brazil
Thiago H. Döring
Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n° 1100, Sao Carlos 13563-120, SP, Brazil
Edgard Marx
Agile Knowledge Engineering and Semantic Web (AKSW), Institute of Computer Science, Leipzig University of Applied Sciences (HTWK), 04109 Leipzig, Germany
Leonardo L. G. Ferreira
Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n° 1100, Sao Carlos 13563-120, SP, Brazil
José L. Medina-Franco
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autonoma de Mexico (UNAM), Avenida Universidad 3000, Mexico City 04510, Mexico
Adriano D. Andricopulo
Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n° 1100, Sao Carlos 13563-120, SP, Brazil
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.
