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Letters in Drug Design & Discovery

Author(s): Daiane Yukie Tezuka, Sergio de Albuquerque, Carlos Alberto Montanari and Andrei Leitão*

DOI: 10.2174/1570180816666191204105232

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

Page: [867 - 872] Pages: 6

  • * (Excluding Mailing and Handling)

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 μM (L. amazonensis), 52 μM (T. cruzi) and 81 μM (T. cruzi), respectively. These molecules were inactive for Balb/C fibroblast cell line at concentrations above 250 μM, 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.

Keywords: Trypanosoma cruzi, Leishmania infantum, Leishmania amazonensis, cell-based assays, selectivity index, antiparasitic compounds.

Graphical Abstract

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