Premium
Synthesis and antimalarial and anticancer evaluation of 7‐chlorquinoline‐4‐thiazoleacetic derivatives containing aryl hydrazide moieties
Author(s) -
Ramírez Hegira,
Fernandez Esteban,
Rodrigues Juan,
Mayora Soriuska,
Martínez Gricelis,
Celis Carmen,
De Sanctis Juan B.,
Mijares Michael,
Charris Jaime
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202100002
Subject(s) - viability assay , chemistry , apoptosis , cell cycle , in vivo , hydrazide , cancer cell , peripheral blood mononuclear cell , cell cycle checkpoint , ic50 , in vitro , stereochemistry , cytotoxicity , cell culture , biochemistry , pharmacology , cancer , biology , organic chemistry , genetics , microbiology and biotechnology
Abstract Twelve 7‐chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2‐[2‐(7‐chloroquinolin‐4‐ylthio)‐4‐methylthiazol‐5‐yl]acetic acid 1 with various benzoyl hydrazines 2a – l . The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of β‐hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC 50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF‐7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF‐7 cells with IC 50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12 . In MCF‐7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.