Abstract
Quantitative structure-activity relationship analysis of some recently synthesized thiourea derivatives was studied for their cytotoxicity data (CC50) in MT-4 cells. The statistically significant 2D-QSAR model-1 (r2 = 0.964, r2 CV = 0.943 and r2 -pred = 0.961) constructed by genetic function approximation (GFA) methodology was obtained when the number of descriptors was set to 4, indicating that the descriptors of the lowest unoccupied orbital energy (LUMO), radius of gyration (RadOfGyration) and E-state indices (S_ssCH2 and S_aaCH) crucially contributed to biological activity. The validation of the model was done by full cross-validation tests, randomization tests and external test set prediction. Molecular field analysis (MFA) on the corresponding training set investigated the substitutional requirements for the favorable receptor-drug interaction using genetic partial least squares (G/PLS) method, showing that both steric and electrostatic fields play a major role in determining activity. The results derived by combining both methodologies may be useful in further prediction of cytotoxity data (CC50) of corresponding anti-HIV drugs.
Keywords: Genetic function approximation, Molecular field analysis, Quantitative structure-activity relationship, Anti-HIV activity, Thiourea derivatives
Letters in Drug Design & Discovery
Title: Quantitative Structure-Activity Relationship Studies on Some Novel Anti- HIV Thiourea Derivatives with Cytotoxicity Data (CC50) in MT-4 Cells
Volume: 6 Issue: 3
Author(s): Ke-Xian Chen, Zu-Guang Li, Hai-Ying Xie and Jian-Rong Gao
Affiliation:
Keywords: Genetic function approximation, Molecular field analysis, Quantitative structure-activity relationship, Anti-HIV activity, Thiourea derivatives
Abstract: Quantitative structure-activity relationship analysis of some recently synthesized thiourea derivatives was studied for their cytotoxicity data (CC50) in MT-4 cells. The statistically significant 2D-QSAR model-1 (r2 = 0.964, r2 CV = 0.943 and r2 -pred = 0.961) constructed by genetic function approximation (GFA) methodology was obtained when the number of descriptors was set to 4, indicating that the descriptors of the lowest unoccupied orbital energy (LUMO), radius of gyration (RadOfGyration) and E-state indices (S_ssCH2 and S_aaCH) crucially contributed to biological activity. The validation of the model was done by full cross-validation tests, randomization tests and external test set prediction. Molecular field analysis (MFA) on the corresponding training set investigated the substitutional requirements for the favorable receptor-drug interaction using genetic partial least squares (G/PLS) method, showing that both steric and electrostatic fields play a major role in determining activity. The results derived by combining both methodologies may be useful in further prediction of cytotoxity data (CC50) of corresponding anti-HIV drugs.
Export Options
About this article
Cite this article as:
Chen Ke-Xian, Li Zu-Guang, Xie Hai-Ying and Gao Jian-Rong, Quantitative Structure-Activity Relationship Studies on Some Novel Anti- HIV Thiourea Derivatives with Cytotoxicity Data (CC50) in MT-4 Cells, Letters in Drug Design & Discovery 2009; 6 (3) . https://dx.doi.org/10.2174/157018009787847828
DOI https://dx.doi.org/10.2174/157018009787847828 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
-
Volatile Disease Biomarkers in Breath: A Critique
Current Pharmaceutical Biotechnology Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants
Current Topics in Medicinal Chemistry Drug Repurposing for the Treatment of Staphylococcal Infections
Current Pharmaceutical Design Cytokine Therapies in Crohns Disease: Where are We Now and where should We Go?
Inflammation & Allergy - Drug Targets (Discontinued) Role of Netrin-1 Beyond the Brain: From Biomarker of Tissue Injury to Therapy for Inflammatory Diseases
Recent Patents on Biomarkers The Immunoproteasome: An Emerging Therapeutic Target
Current Topics in Medicinal Chemistry Identification of Phosphoinositide-3 Kinases Delta and Gamma Dual Inhibitors Based on the p110δ/γ Crystal Structure
Letters in Drug Design & Discovery Is There a Genetic Susceptibility to Bronchopulmonary Dysplasia?
Current Respiratory Medicine Reviews Bee Venom: Its Potential Use in Alternative Medicine
Anti-Infective Agents Application of High Hydrostatic Pressure to Dissociate Aggregates and Refold Proteins
Current Pharmaceutical Biotechnology Animal Models of Lung Fibrosis
Current Respiratory Medicine Reviews Role of β 2-Adrenoceptor Activation in Sepsis-Induced Renal Inflammation
Current Immunology Reviews (Discontinued) Synthesis and Evaluation of Compounds Containing 4-arylpiperazinyl Moieties Linked to a 2-(pyridin-3-yl)-1H-benzimidazole as p38 MAP Kinase Inhibitors
Letters in Drug Design & Discovery The Prevalence of the Classical and Non-Classical Cardiovascular Risk Factors in Multiple Sclerosis Patients
CNS & Neurological Disorders - Drug Targets Metabolic Syndrome and Asthma
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1 ?
Current Drug Targets Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise
Current Pharmaceutical Design Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery Ethanol and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Blocking Leukocyte Rolling: Does it have a Role in Disease Prevention?
Vascular Disease Prevention (Discontinued)