Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds.

Autor: Maranhão SS; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil., Moura AF; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil., Oliveira ACA; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil., Lima DJB; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil., Barros-Nepomuceno FWA; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil; Institute of Health Sciences, University for International Integration of the Afro-Brazilian Lusophony, CE 060, Km 51, CEP 62785-000 Acarape, CE, Brazil., Paier CRK; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil., Pinheiro AC; Oswaldo Cruz Foundation, Institute of Technology in Drugs - Farmanguinhos, 21041-250 Rio de Janeiro, RJ, Brazil., Nogueira TCM; Oswaldo Cruz Foundation, Institute of Technology in Drugs - Farmanguinhos, 21041-250 Rio de Janeiro, RJ, Brazil., de Souza MVN; Oswaldo Cruz Foundation, Institute of Technology in Drugs - Farmanguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; Federal University of Rio de Janeiro, Institute of Chemistry, Department of Organic Chemistry, CP 68563, 21945-970 Rio de Janeiro, RJ, Brazil., Pessoa C; Laboratory of Experimental Oncology, Center for Research and Drug Development, Federal University of Ceará, Rua Coronel Nunes de Melo 1000, CEP 60430-275 Fortaleza, CE, Brazil. Electronic address: cpessoa@ufc.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Jan 15; Vol. 30 (2), pp. 126851. Date of Electronic Publication: 2019 Dec 03.
DOI: 10.1016/j.bmcl.2019.126851
Abstrakt: Quinoxaline derivatives are reported as antineoplastic agents against a variety of human cancer cell lines, with some compounds being submitted to clinical trials. In this work, we report the synthesis, characterization and cytotoxicity potential of a new series of quinoxalinyl-hydrazones. The most cytotoxic compound was (E)-2-[2-(2-pyridin-2-ylmethylene)hydrazinyl]quinoxaline (PJOV56) that presented a time-dependent effect against HCT-116 cells. After 48 h of incubation, PJOV56 was able to induce autophagy and apoptosis of HCT-116 cells, mediated by upregulation of Beclin 1, upregulation of LC3A/B II and activation of caspase 7. Apoptosis was induced along with G0/G1 cell cycle arrest at the highest concentration of PJOV56 (6.0 µM). Thus, PJOV56 showed a dose-dependent mode of action related to induction of autophagy and apoptosis in HCT-116 cells.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: