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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Tezuka, Daiane Yukie [1, 2] ; de Albuquerque, Sergio [3] ; Montanari, Carlos Alberto [1] ; Leitao, Andrei [1, 2]
Total Authors: 4
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
Total Affiliations: 3
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 type: 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 type: Regular Research Grants