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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.)

Cytotoxicity of 4-substituted quinoline derivatives: Anticancer and antileishmanial potential

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Costa, Claudia A. [1] ; Lopes, Rayssa M. [1] ; Ferraz, Leticia S. [2] ; Esteves, Gabriela N. N. [2] ; Di Iorio, Juliana F. [1] ; Souza, Aline A. [1] ; de Oliveira, Isadora M. [3] ; Manarin, Flavia [4] ; Judice, Wagner A. S. [1] ; Stefani, Helio A. [5] ; Rodrigues, Tiago [2]
Total Authors: 11
[1] Univ Mogi das Cruzes UMC, Ctr Interdisciplinar Invest Bioquim CIIB, Mogi Das Cruzes, SP - Brazil
[2] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas CCNH, Santo Andre, SP - Brazil
[3] Univ Sao Paulo, Inst Quim IQ, Dept Quim Fundamental, Sao Paulo, SP - Brazil
[4] Univ Estadual Oeste Parana, Ctr Engn & Ciencias Exatas CECE, Toledo, PR - Brazil
[5] Univ Sao Paulo, Dept Farm, Fac Ciencias Farmaceut FCF, Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Bioorganic & Medicinal Chemistry; v. 28, n. 11 JUN 1 2020.
Web of Science Citations: 0

Chemical modifications of quinoline moiety have been recognized as a useful strategy to development of new drugs. Here, the cytotoxicity of a set of twenty-four 4-substituted quinolines (named HTI) was screened for their antitumor and antileishmanial potential in vitro, and the underlying mechanisms investigated. HTI 21 and HTI 22 exhibited the highest cytotoxicity, being selected to the subsequent studies. Both derivatives induced caspase-dependent apoptosis associated to the dissipation of the mitochondrial transmembrane potential (Delta psi) and ROS generation. HTI-induced cell death was calcium dependent, associated to thiol oxidation and cysteine proteases activation. In isolated mitochondria, HTI derivatives promoted mitochondrial permeabilization by different mechanisms. The inhibition of BCL-2 by venetoclax enhanced the HTI-induced cytotoxicity. Regarding the inhibition of cysteine proteases type B of Leishmania mexicana, HTI 15 exhibited the most potent inhibitory activity through a linear non-competitive mechanism. These data highlight the therapeutic potential of 4-substituted quinolines as antitumor and antileishmanial drugs. (AU)

FAPESP's process: 16/04289-3 - Synthesis of calcogeno amino acids derivatives and 4-calcogeno quinolines via multicomponent reactions
Grantee:Isadora Maria de Oliveira
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/25747-5 - Alterations of mitochondrial morphology and dynamics in cancer: understanding of tumor biology and prospecting new therapeutic targets
Grantee:Tiago Rodrigues
Support type: Regular Research Grants
FAPESP's process: 16/25112-4 - Evaluation of modulators of the activity of proteases involved in pathological processes
Grantee:Wagner Alves de Souza Júdice
Support type: Regular Research Grants
FAPESP's process: 17/24821-4 - Carbonylative Coupling and Intramolecular Cycloaddition [2 + 2] Reactions Employing D-Glucal
Grantee:Helio Alexandre Stefani
Support type: Regular Research Grants
FAPESP's process: 14/02205-1 - Study of kinetic behavior of convertases
Grantee:Wagner Alves de Souza Júdice
Support type: Regular Research Grants