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Microwave‐assisted synthesis of 2‐styrylquinoline‐4‐carboxylic acid derivatives to improve the toxic effect against Leishmania (Leishmania) amazonensis
Author(s) -
Luczywo Ayelen,
Sauter Ismael Pretto,
Silva Ferreira Thalita Camêlo,
Cortez Mauro,
Romanelli Gustavo P.,
Sathicq Gabriel,
Asís Silvia E.
Publication year - 2021
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4217
Subject(s) - chemistry , quinoline , leishmania , amastigote , intracellular , leishmaniasis , cytotoxicity , moiety , intracellular parasite , kinetoplastida , biological activity , cutaneous leishmaniasis , macrophage , carboxylic acid , microbiology and biotechnology , biochemistry , parasite hosting , in vitro , stereochemistry , organic chemistry , trypanosoma cruzi , immunology , biology , world wide web , computer science
The identification of new compounds is urgent to develop safe and efficacious candidates for leishmaniasis treatment, especially from natural products as a potential source of active molecules against neglected tropical parasite diseases. Inspired by the efficacious quinoline alkaloid microbial effects, we have previously reported the synthesis and biological activity of 2‐phenylquinoline‐4‐carboxylic acids and poly‐substituted quinolines against parasites. In this work, a series of eighteen 2‐styryl‐4‐quinolinecarboxylic acids were synthesized under microwave irradiation settings obtaining from good to excellent yields (60%‐90%), shorter reaction times (2 minutes), and eco‐friendly experimental conditions. All these products were evaluated against infective forms of Leishmania (Leishmania) amazonensis , such as promastigotes and intracellular amastigotes, based on cytotoxicity assays, including host macrophage infection assays. Compounds 4 and 5 possessing a 2‐chloro or 4‐chlorostyryl moiety, respectively, were considered the most promising antileishmanial agents due to the parasite killing effect in intracellular forms inside infected macrophages. Thus, our results revealed that the 2‐styryl‐4‐quinolinecarboxylic acid backbone structure was essential for the activity against intracellular pathogens like L. (L.) amazonensis .