Discovery of 2-aminopyridine Derivatives with Antichagasic and Antileishmanial Activity Using Phenotypic Assays

Autor(es)

Tezuka, Daiane Yukie ^{[1, 2]} ; de Albuquerque, Sergio ^[3] ; Montanari, Carlos Alberto ^[1] ; Leitao, Andrei ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Chem Grp NEQUIMED, Sao Carlos Inst Chem IQSC, Sao Paulo - Brazil

^[2] Programa Posgrad Bioengn EESC USP, Sao Paulo - Brazil

^[3] Univ Sao Paulo FCFRP USP, Lab Parasitol, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: LETTERS IN DRUG DESIGN & DISCOVERY; v. 17, n. 7, p. 867-872, 2020.
• Citações Web of Science: 0

Resumo

Background: Compounds previously studied as anticancer were screened against trypomastigotes to access the bioactivity. The epimastigote form of Trypanosoma cruzi Y strain and the promastigote form of Leishmania amazonensis and Leishmania infantum were used in this work. Methods: Cell-based assays were performed to access the bioactivity of the compounds using MTT and the flow cytometry methods. Results: Neq0438, Neq0474 and Neq0440 had the highest potency, with EC50 of 39 mu M (L. amazonensis), 52 mu M (T. cruzi) and 81 mu M (T. cruzi), respectively. These molecules were inactive for Balb/C fibroblast cell line at concentrations above 250 mu M, showing selectivity for the parasites. Conclusion: This is the first report that demonstrates antiparasitic activity for the 2-aminopyridine scaffold, with cross-activity against cancer cells. (AU)

• Processo FAPESP: 13/18009-4 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína
• Beneficiário: Carlos Alberto Montanari
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/15904-6 - Caracterização de inibidores de cisteíno proteases com atividade antineoplásica por meio de ensaios in silico, celulares e análise química
• Beneficiário: Andrei Leitão
• Modalidade de apoio: Auxílio à Pesquisa - Regular