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

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

  • Bioorg Med Chem Lett. 2020 Jan 15;30(2):126851. doi: 10.1016/j.bmcl.2019.126851.
Sarah Sant'Anna Maranhão 1,  Andrea Felinto Moura 1,  Augusto César Aragão Oliveira 1,  Daisy Jereissati Barbosa Lima 1,  Francisco Washington Araújo Barros-Nepomuceno 2,  Carlos Roberto Koscky Paier 1,  Alessandra Campbell Pinheiro 3,  Thais Cristina Mendonça Nogueira 3,  Marcus Vinícius Nora de Souza 4,  Claudia Pessoa 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Oswaldo Cruz Foundation, Institute of Technology in Drugs - Farmanguinhos, 21041-250 Rio de Janeiro, RJ, Brazil.
  • 4 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.
  • 5 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.
PMID: 31836446 DOI: 10.1016/j.bmcl.2019.126851
Abstract

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.

Keywords

Cell cycle arrest; Cytotoxicity; HCT-116 cells; Quinoxalines.

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