Abstract
For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r2) and prediction accuracy (rCV2) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.
Keywords: 18β-glycyrrhetinic acid, QSAR, Docking, Drug likeness, Human lung cancer (A-549), in-vitro cytotoxicity.
Medicinal Chemistry
Title:QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 β-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549
Volume: 9 Issue: 8
Author(s): Dharmendra Kumar Yadav, Komal Kalani, Feroz Khan and Santosh Kumar Srivastava
Affiliation:
Keywords: 18β-glycyrrhetinic acid, QSAR, Docking, Drug likeness, Human lung cancer (A-549), in-vitro cytotoxicity.
Abstract: For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r2) and prediction accuracy (rCV2) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.
Export Options
About this article
Cite this article as:
Yadav Kumar Dharmendra, Kalani Komal, Khan Feroz and Srivastava Kumar Santosh, QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 β-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549, Medicinal Chemistry 2013; 9 (8) . https://dx.doi.org/10.2174/1573406411309080009
DOI https://dx.doi.org/10.2174/1573406411309080009 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Current Status and Future Perspectives of PI3K and mTOR Inhibitor as Anticancer Drugs in Breast Cancer
Current Cancer Drug Targets Future Prospect of RNA Interference for Cancer Therapies
Current Drug Targets Bitter Gourd (Momordica charantia) is a Cornucopia of Health: A Review of its Credited Antidiabetic, Anti-HIV, and Antitumor Properties
Current Molecular Medicine Emerging Roles of P2X Receptors in Cancer
Current Medicinal Chemistry MEK Inhibitors: A Therapeutic Approach to Targeting the Ras-MAP Kinase Pathway in Tumors
Current Pharmaceutical Design PI3K/Akt/mTOR Pathway Inhibitors in Cancer: A Perspective on Clinical Progress
Current Medicinal Chemistry Accuracy of a Topical PET/CT Scanner on SUV Measurements of Small Volumes SUV
Current Medical Imaging Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer
Anti-Cancer Agents in Medicinal Chemistry Pharmaceutical Strategies Enhancing Cell Penetration Efficiencies of Non-Viral Gene Delivery Systems
Current Gene Therapy Cell-free DNA: Characteristics, Detection and its Applications in Myocardial Infarction
Current Pharmaceutical Design Cytotoxic and Allergenic Potential of Bioactive Proteins and Peptides
Current Pharmaceutical Design Vasoproliferation and Antiproliferative Treatment Options in Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Mechanisms of Tumor Cell Necrosis
Current Pharmaceutical Design Anti-Cancer Effect of Melatonin via Downregulation of Delta-like Ligand 4 in Estrogen-Responsive Breast Cancer Cells
Recent Patents on Anti-Cancer Drug Discovery Cognitive Impairment in Systemic Lupus Erythematosus: Prevalence and Clinical Importance
Current Rheumatology Reviews Current Perspectives on Novel Drug Delivery Systems and Therapies for Management of Prostate Cancer: An Inclusive Review
Current Drug Targets Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery
Combinatorial Chemistry & High Throughput Screening MicroRNA-34a Promotes Cardiomyocyte Apoptosis Post Myocardial Infarction Through Down-regulating Aldehyde Dehydrogenase 2
Current Pharmaceutical Design Tailored Mesoporous Silica Nanoparticles for Controlled Drug Delivery: Platform Fabrication, Targeted Delivery, and Computational Design and Analysis
Mini-Reviews in Medicinal Chemistry The Roles of miR-25 and its Targeted Genes in Development of Human Cancer
MicroRNA