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

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.

• Authors: 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
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 30 Issue 2 Pg. 126851 (01 15 2020) ISSN: 1464-3405 [Electronic] England
• PMID: 31836446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Hydrazones
• Quinoxalines

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Colorectal Neoplasms (drug therapy)
• Humans
• Hydrazones (chemical synthesis, chemistry)
• Quinoxalines (chemical synthesis, chemistry)
• Structure-Activity Relationship