Abstract
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 on 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 on 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.Keywords: Quinoxaline 1, 4-di-N-oxide, anti-cancer, apoptosis, QSAR, DFT.
Anti-Cancer Agents in Medicinal Chemistry
Title:Ester of Quinoxaline-7-carboxylate 1,4-di-N-oxide as Apoptosis Inductors in K-562 Cell Line: An in vitro, QSAR and DFT Study
Volume: 17 Issue: 5
Author(s): Gildardo Rivera, Sergio Andrade-Ochoa, Manolo S. Ortega Romero, Isidro Palos, Antonio Monge and Luvia Enid Sanchez-Torres*
Affiliation:
- Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F.,Mexico
Keywords: Quinoxaline 1, 4-di-N-oxide, anti-cancer, apoptosis, QSAR, DFT.
Abstract: 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 on 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 on 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.Export Options
About this article
Cite this article as:
Rivera Gildardo, Andrade-Ochoa Sergio, Romero S. Ortega Manolo, Palos Isidro, Monge Antonio and Sanchez-Torres Enid Luvia*, Ester of Quinoxaline-7-carboxylate 1,4-di-N-oxide as Apoptosis Inductors in K-562 Cell Line: An in vitro, QSAR and DFT Study, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (5) . https://dx.doi.org/10.2174/1871520616666160630175927
DOI https://dx.doi.org/10.2174/1871520616666160630175927 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Systemic Approach to the Study of Complex Bone Disorders at the Whole- Genome Level
Current Genomics Colon as Target for Drug Delivery
Current Drug Therapy Chemistry and Structural Evaluation of Different Phospholipase A2 Inhibitors in Arachidonic Acid Pathway Mediated Inflammation and Snake Venom Toxicity
Current Topics in Medicinal Chemistry Gene Expression Signatures of Lymph Node Metastasis in Oral Cancer: Molecular Characteristics and Clinical Significances
Current Cancer Therapy Reviews Structure Based Drug Design and Molecular Docking Studies of Anticancer Molecules Paclitaxel, Etoposide and Topotecan using Novel Ligands
Current Drug Discovery Technologies Walking the Oxidative Stress Tightrope: A Perspective from the Naked Mole-Rat, the Longest-Living Rodent
Current Pharmaceutical Design Redox-Sensitive Smart Nanosystems for Drug and Gene Delivery
Current Organic Chemistry Clinical Development of MET Targeted Therapy For Human Cancer
Current Cancer Therapy Reviews Neglected Tropical Protozoan Diseases: Drug Repositioning as a Rational Option
Current Topics in Medicinal Chemistry Cancer Multitarget Pharmacology in Prostate Tumors: Tyrosine Kinase Inhibitors and Beyond
Current Medicinal Chemistry Pharmaceutical Polymeric Nanoparticles Prepared by the Double Emulsion- Solvent Evaporation Technique
Recent Patents on Drug Delivery & Formulation Peptides or Small Molecules? Different Approaches to Develop More Effective CDK Inhibitors
Current Medicinal Chemistry Using Insights into Pim1 Structure to Design New Anticancer Drugs
Current Pharmaceutical Design Backbone-Cyclized Peptides: A Critical Review
Current Topics in Medicinal Chemistry Clinico-Pathologic and Biologic Predictors of EGFR Inhibitors Activity and Efficacy in Lung and in Colorectal Cancer
Current Signal Transduction Therapy Germinated Soybean Products as Nutraceutical Compounds in Breadmaking
Current Nutrition & Food Science Anti-tumorigenic Efficacy of Tangeretin in Liver Cancer – An In Silico Approach
Current Computer-Aided Drug Design Humoral and Mechanical Cross-Talk in the Vasculature: Perspectives in Vascular Disease
Vascular Disease Prevention (Discontinued) An Update on Natural Occurrence and Biological Activity of Chromones
Current Medicinal Chemistry Cancer Therapy-Induced Residual Bone Marrow Injury: Mechanisms of Induction and Implication for Therapy
Current Cancer Therapy Reviews