TY - JOUR
T1 - Ester of quinoxaline-7-carboxylate 1,4-di-N-oxide as apoptosis inductors in K-562 cell line
T2 - An in vitro, QSAR and DFT study
AU - Rivera-Sánchez, Gildardo
AU - Andrade-Ochoa, Sergio
AU - Ortega Romero, Manolo S.
AU - Palos, Isidro
AU - Monge, Antonio
AU - Sánchez-Torres, Luvia Enid
N1 - Publisher Copyright:
© 2016 Bentham Science Publishers.
PY - 2016
Y1 - 2016
N2 - Background: Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives in K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models. Material and Methods: Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor activity in K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms. Results & Conclusions: Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed.
AB - Background: Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives in K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models. Material and Methods: Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor activity in K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms. Results & Conclusions: Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed.
KW - 4-di-N-oxide
KW - Anti-cancer
KW - Apoptosis
KW - QSAR
KW - Quinoxaline 1
UR - http://www.scopus.com/inward/record.url?scp=85020274638&partnerID=8YFLogxK
U2 - 10.2174/1871520616666160630175927
DO - 10.2174/1871520616666160630175927
M3 - Artículo
C2 - 27396382
SN - 1871-5206
VL - 16
SP - 682
EP - 691
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
ER -