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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: LETTERS IN DRUG DESIGN & DISCOVERY; v. 17, n. 7, p. 867-872, 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/18009-4 - Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors
• Grantee: Carlos Alberto Montanari
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/15904-6 - Characterization of cysteine protease inhibitors with antineoplastic activity by in silico and cell-based assays coupled with chemical analyses
• Grantee: Andrei Leitão
• Support Opportunities: Regular Research Grants