In silico-driven identification of novel molluscicides effective against Biomphalaria glabrata (Say, 1818)

Autor(es)

Santos, Daniela Braz dos ^[1] ; Moreira-Filho, Jose Teofilo ^{[1, 2]} ; Melo, Amanda de Oliveira ^[3] ; Lemes, Josiel Araujo ^[3] ; Damacena Silva, Luciana ^[4] ; Rocha, Thiago Lopes ^[5] ; Andrade, Carolina Horta ^[2] ; Neves, Bruno Junior ^[2] ; Bezerra, Jose Clecildo Barreto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Goias, Inst Patol Trop & Saude Publ, Lab Studies Host Parasite Relationship, Goiania, Go - Brazil

^[2] Univ Fed Goias, Fac Farm, LabMol Lab Mol Modeling & Drug Design, Goiania, Go - Brazil

^[3] Ctr Univ Anapolis UniEVANGE LICA, Lab Cheminformat, Anapolis, Go - Brazil

^[4] Univ Estadual Goias, Lab Host Parasite Interact, Anapolis, Go - Brazil

^[5] Univ Fed Goias, Lab Environm Biotechnol & Ecotoxicol, Inst Patol Trop & Saude Publ, Goiania, Go - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEW JOURNAL OF CHEMISTRY; v. 44, n. 39, p. 16948-16958, OCT 21 2020.
• Citações Web of Science: 0

Resumo

Schistosomiasis control in endemic areas depends on several factors, including mass drug delivery programs and interrupting the transmission of disease by controlling the intermediate host snails in the freshwater ecosystem using molluscicides. However, the use of the gold standard molluscicide,i.e., niclosamide, has been considered problematic due to its high cost, toxicity for aquatic organisms, and the emergence of niclosamide-resistant snail populations. In this work, we report thein silicodriven identification of novel naphthoquinone compounds with high molluscicidal activity againstBiomphalaria glabrata. For this purpose, we developed statistically robust and validated shape-based and machine learning models usingB. glabratabioassay compounds data. Using these models, we prioritized fourteen naphthoquinone compounds for furtherin vivotesting against adult, newly-hatched, and embryo ofB. glabratasnails. Among them, compounds3,5,6,7, and12were the best candidates, presenting moderate potency against adult snails (LC50: 28.98-102.24 mu M) and high potency (LC50: 14.52-0.45 mu M) against newly-hatched snails and embryos. To summarize, thein silicoapproach explored here allowed us to discover five new molluscicidal candidates for prospective field studies. (AU)

• Processo FAPESP: 17/02353-9 - Bioinformática, Quimiogenômica e Quimioinformática aplicados à Descoberta de Novos Fármacos e Produtos Biotecnológicos
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Brasil