Abstract
P-glycoprotein (P-gp) is responsible for the multidrug resistance (MDR) and involved in the expulsion of xenobiotics out of cell. In this paper, homology modeling, docking and molecular dynamics simulation (MDS) was performed for the human P-gp desmosdumotin inhibitor. Docking study was carried out in the P-gp nucleotide binding domain 2 (NBD2). The desmosdumotin binding region occupied the ATP binding region (flavonoid binding region) with hydrophobic and hydrophilic interactions. Analysis of root mean square deviations (RMSDs) of active site residues indicated the binding site residues were stable throughout the simulation period. As shown in previous results with structurally similar flavonoid compounds, van der Waals and electrostatic interactions were found to be important factors for the desmosdumotin-NBD2 inhibition. Docking results suggest that desmosdumotin interacts with the NBD2 through both hydrogen bonds (Lys1076, Ser1077 and Thr1078) and hydrophobic interactions (Tyr1044, Val1052, Gly1073 and Cys1074). In addition, the involvement of other amino-acids was identified via MDS (Lys1076 and Ser1077 for hydrogen bonds and Tyr1044, Val1052, Gly1073, Cys1074 and Gly1075 for hydrophobic interactions). Thus, current preliminary model of interactions between desmosdumotin-NBD2 could be helpful to understand the in-depth inhibition mechanism of P-gp at NBD2 level and to design more potent inhibitors which could effectively overcome MDR of anticancer agents.
Keywords: Anti-cancer agent, desmosdumotin, docking, dynamic simulation, homology modeling, NBD2, P-gp.
Anti-Cancer Agents in Medicinal Chemistry
Title:In Silico Study of Desmosdumotin as an Anticancer Agent: Homology Modeling, Docking and Molecular Dynamics Simulation Approach
Volume: 13 Issue: 10
Author(s): Changdev G. Gadhe, Gugan Kothandan and Seung Joo Cho
Affiliation:
Keywords: Anti-cancer agent, desmosdumotin, docking, dynamic simulation, homology modeling, NBD2, P-gp.
Abstract: P-glycoprotein (P-gp) is responsible for the multidrug resistance (MDR) and involved in the expulsion of xenobiotics out of cell. In this paper, homology modeling, docking and molecular dynamics simulation (MDS) was performed for the human P-gp desmosdumotin inhibitor. Docking study was carried out in the P-gp nucleotide binding domain 2 (NBD2). The desmosdumotin binding region occupied the ATP binding region (flavonoid binding region) with hydrophobic and hydrophilic interactions. Analysis of root mean square deviations (RMSDs) of active site residues indicated the binding site residues were stable throughout the simulation period. As shown in previous results with structurally similar flavonoid compounds, van der Waals and electrostatic interactions were found to be important factors for the desmosdumotin-NBD2 inhibition. Docking results suggest that desmosdumotin interacts with the NBD2 through both hydrogen bonds (Lys1076, Ser1077 and Thr1078) and hydrophobic interactions (Tyr1044, Val1052, Gly1073 and Cys1074). In addition, the involvement of other amino-acids was identified via MDS (Lys1076 and Ser1077 for hydrogen bonds and Tyr1044, Val1052, Gly1073, Cys1074 and Gly1075 for hydrophobic interactions). Thus, current preliminary model of interactions between desmosdumotin-NBD2 could be helpful to understand the in-depth inhibition mechanism of P-gp at NBD2 level and to design more potent inhibitors which could effectively overcome MDR of anticancer agents.
Export Options
About this article
Cite this article as:
Gadhe G. Changdev, Kothandan Gugan and Cho Joo Seung, In Silico Study of Desmosdumotin as an Anticancer Agent: Homology Modeling, Docking and Molecular Dynamics Simulation Approach, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/18715206113139990302
DOI https://dx.doi.org/10.2174/18715206113139990302 |
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
-
Remote Ischemic Conditioning Improves Cognitive Function During Cerebral Vascular Injury Through the Induction of Autophagy
Current Neurovascular Research A Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan
Current Cancer Drug Targets 64Cu Labeled AmBaSar-RGD2 for micro-PET Imaging of Integrin αvβ3 Expression
Current Radiopharmaceuticals Paving the Way to Personalized Genomic Medicine: Steps to Successful Implementation
Current Pharmacogenomics and Personalized Medicine Molecule of the Month
Current Topics in Medicinal Chemistry Green Tea Catechins: Proposed Mechanisms of Action in Breast Cancer Focusing on the Interplay Between Survival and Apoptosis
Anti-Cancer Agents in Medicinal Chemistry A Review on Biomedical Applications of Single-Walled Carbon Nanotubes
Current Medicinal Chemistry Glyoxalase Pathway of Trypanosomatid Parasites: A Promising Chemotherapeutic Target
Current Drug Targets A Systematic Evaluation of Solubility Enhancing Excipients to Enable the Generation of Permeability Data for Poorly Soluble Compounds in Caco-2 Model
Drug Metabolism Letters Roles of Laminin-332 and α6β4 Integrin in Tumor Progression
Mini-Reviews in Medicinal Chemistry Contemporary Progress in the Synthesis and Reaction of 2-Arylbenzothiazole: A Review
Current Organic Chemistry Quantitative Determination of a Novel Pseudoalkaloid Colchatetralene Isolated from the Mycoflora of Gloriosa superba Linn by HPTLC
The Natural Products Journal Folate-Linked Lipid-Based Nanoparticle for Targeted Gene Delivery
Current Drug Delivery The Detection of Pb<sup>2+</sup> Using Glutathione Capped Mn Doped ZnS QDs
Current Analytical Chemistry Advances in Chondroitin Sulfate Analysis: Application in Physiological and Pathological States of Connective Tissue and During Pharmacological Treatment of Osteoarthritis
Current Pharmaceutical Design Photocatalytic Activities, Kinetics and Adsorption Isotherm Studies of CeO2 Nanoparticles Synthesized via Low Temperature Combustion Method
Current Nanomaterials Modulation of TRAIL-Induced Apoptosis by HDAC Inhibitors
Current Cancer Drug Targets Targeting EGFR and HER2 with 211At-Labeled Molecules: Unexpected and Expected Dose-Effect Relations in Cultured Tumor Cells
Current Radiopharmaceuticals A Review of Fish Lectins
Current Protein & Peptide Science Biotechnologically Produced Secondary Plant Metabolites for Cancer Treatment and Prevention
Current Pharmaceutical Biotechnology