| Autor: |
Valli M; 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.; School of Pharmaceutical Sciences of Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Avenida Professor Doutor Zeferino Vaz, s/n, Ribeirao Preto 14040-903, SP, Brazil., Döring TH; 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.; Department of Exact Sciences and Education (CEE), School of Technology, Exact Sciences and Education (CTE), Federal University of Santa Catarina (UFSC), Blumenau 89036-256, SC, Brazil., Marx E; Agile Knowledge Engineering and Semantic Web (AKSW), Institute of Computer Science, Leipzig University of Applied Sciences (HTWK), 04109 Leipzig, Germany., Ferreira LLG; 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., Medina-Franco JL; DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autonoma de Mexico (UNAM), Avenida Universidad 3000, Mexico City 04510, Mexico., Andricopulo AD; 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. |
| Abstrakt: |
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. |
