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.
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.
Bioorg Med Chem Lett. 2020 Jan 15;30(2):126851. doi: 10.1016/j.bmcl.2019.126851. Epub 2019 Dec 3.
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.
喹喔啉衍生物被报道具有抗肿瘤活性，可对抗多种人类癌细胞系，其中一些化合物已进入临床试验。在这项工作中，我们报告了一系列新型喹喔啉腙的合成、表征和细胞毒性潜力。最具细胞毒性的化合物是(E)-2-[2-(2-吡啶-2-亚甲基)肼基]喹喔啉(PJOV56)，它对 HCT-116 细胞表现出时间依赖性效应。孵育 48 小时后，PJOV56 能够通过上调 Beclin 1、上调 LC3A/B II 和激活 caspase 7 诱导 HCT-116 细胞自噬和凋亡。在 PJOV56 的最高浓度（6.0 μM）下，细胞凋亡伴随着 G0/G1 细胞周期停滞。因此，PJOV56 在诱导 HCT-116 细胞自噬和凋亡方面表现出剂量依赖性作用模式。
