1. Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds.
- Author
-
Maranhão SS, Moura AF, Oliveira ACA, Lima DJB, Barros-Nepomuceno FWA, Paier CRK, Pinheiro AC, Nogueira TCM, de Souza MVN, and Pessoa C
- Subjects
- Humans, Hydrazones chemistry, Quinoxalines chemistry, Structure-Activity Relationship, Apoptosis drug effects, Autophagy drug effects, Colorectal Neoplasms drug therapy, Hydrazones chemical synthesis, Quinoxalines chemical synthesis
- 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF