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

Sarah Sant'Anna Maranhão; Andrea Felinto Moura; Augusto César Aragão Oliveira; Daisy Jereissati Barbosa Lima; Francisco Washington Araújo Barros-Nepomuceno; Carlos Roberto Koscky Paier; Alessandra Campbell Pinheiro; Thais Cristina Mendonça Nogueira; Marcus Vinícius Nora de Souza; Claudia Pessoa

doi:10.1016/j.bmcl.2019.126851

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. Epub 2019 Dec 3.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Autophagy / drug effects*
Colorectal Neoplasms / drug therapy*
Humans
Hydrazones / chemical synthesis*
Hydrazones / chemistry
Quinoxalines / chemical synthesis*
Quinoxalines / chemistry
Structure-Activity Relationship

Substances

Hydrazones
Quinoxalines