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 |
- 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
-
Circulating Tumor Cells in Cancer Therapy: Are we off Target?
Current Cancer Drug Targets Editorial [ Hot Topic:Biology in Anticancer Treatment (Guest Editor: Bruno Vincenzi)]
Current Cancer Drug Targets Mesoporous Materials Used in Medicine and Environmental Applications
Current Topics in Medicinal Chemistry High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics
Current Drug Targets Particle Design of Membrane Emulsification for Protein Drug and Vaccine Delivery
Current Pharmaceutical Design PEGylated Lipid Nanocapsules with Improved Drug Encapsulation and Controlled Release Properties
Current Topics in Medicinal Chemistry A novel NGR-conjugated peptide targets DNA damage responses for radiosensitization
Current Cancer Drug Targets Malignant Mesothelioma: Biology, Diagnosis and Therapeutic Approaches
Current Molecular Pharmacology Combining Chemotherapy with Immunotherapy in Colorectal Cancer: A Review
Clinical Cancer Drugs Glycosylation of Tetraspanin Tspan-1 at Four Distinct Sites Promotes Its Transition Through the Endoplasmic Reticulum
Protein & Peptide Letters Chitosan and Quercetin: Potential Hand in Hand Encountering Tumors in Oral Delivery System
Current Pharmaceutical Design Withanolides: Biologically Active Constituents in the Treatment of Alzheimer’s Disease
Medicinal Chemistry Biology and Impact of Signal Transducers and Activators of Transcription and Their Regulators as Targets in Cancer Therapy
Current Signal Transduction Therapy Editorial: The microRNA 221/222 Cluster: Inaugurating a New Era in Cardiovascular Disease and Cancer?
Current Vascular Pharmacology Allosteric Inhibitors of Bcr-Abl: Towards Novel Myristate-Pocket Binders
Current Pharmaceutical Biotechnology Trends in Malignant Glioma Monoclonal Antibody Therapy
Current Cancer Therapy Reviews Inhibitors of Lactate Dehydrogenase Isoforms and their Therapeutic Potentials
Current Medicinal Chemistry Targeted Gene Therapy for Ovarian Cancer
Current Gene Therapy Cyclooxygenases in Cancer: Chemoprevention and Sensitization to Conventional Therapies
Mini-Reviews in Medicinal Chemistry Morpho-Functional Features of In-Vitro Cell Death Induced by Physical Agents
Current Pharmaceutical Design