RESUMO
Correction for 'O2-(6-Oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolates: a new class of nitric oxide donors activatable by GSH/GSTπ with both anti-proliferative and anti-metastatic activities against melanoma' by Chengfeng Bai et al., Chem. Commun., 2017, 53, 5059-5062.
RESUMO
The new nitric oxide (NO) donor O2-(6-oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolate 3c could simultaneously liberate NO as well as an active 3-glutathionyl-2-exomethylene-cyclohexanone 2 in the presence of GSH/GSTπ; exhibit potent antiproliferative activity; repress migration, invasion, and lateral migration of metastatic B16-BL6 cells; and significantly decrease hetero-adhesion of B16-BL6 cells to human umbilical vein endothelial cells.
Assuntos
Antineoplásicos/farmacologia , Compostos Aza/química , Cicloexenos/farmacologia , Glutationa Transferase/metabolismo , Glicosídeo Hidrolases/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/patologia , Metástase Neoplásica/tratamento farmacológico , Óxido Nítrico/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cicloexenos/química , Cicloexenos/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Microscopia de Fluorescência , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/metabolismo , Metástase Neoplásica/patologia , Relação Estrutura-AtividadeRESUMO
Multidrug resistance is a major obstacle to successful chemotherapy for leukemia. In this study, a series of nitric oxide (NO)-releasing bifendate derivatives (7a-n) were synthesized. Biological evaluation indicated that the most active compound (7a) produced relatively high levels of NO and significantly inhibited the proliferation of drug-resistant K562/A02 cells in vitro and in vivo. In addition, 7a induced the mitochondrial tyrosine nitration and the intracellular accumulation of rhodamine 123 by inhibiting P-gp activity in K562/A02 cells. Furthermore, 7a remarkably down-regulated AKT, NF-κB, and ERK activation and HIF-1α expression in K562/A02 cells, which are associated with the tumor cell proliferation and drug resistance. Notably, the antitumor effects were dramatically attenuated by an NO scavenger or elimination of the NO-releasing capability of 7a, indicating that NO produced by 7a contributed to, at least partly, its cytotoxicity against drug-resistant K562/A02 cells. Overall, 7a may be a potential agent against drug-resistant myelogenous leukemia.
Assuntos
Compostos de Bifenilo/farmacologia , Óxido Nítrico/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Xenoenxertos , Humanos , Técnicas In Vitro , Células K562 , Camundongos , Camundongos NusRESUMO
A novel class of O2-(2,4-dinitrophenyl)-1-[N,N-bis(2-substituted ethyl)amino]diazen-1-ium-1,2-diolates 4-6 were designed, synthesized, and biologically evaluated. The most active compound 6 caused significant DNA damage by releasing N,N-bis(2-TsO ethyl)amine and two molecules of nitric oxide (NO) after activation by GST/GSH in cancer cells, being more cytotoxic against three cancer cell lines than a well-known diazeniumdiolate-based anticancer agent JS-K, suggesting that the strategy has potential to extend to other O2-derived diazeniumdiolates to improve anticancer activity.