Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

In Silico Study of Desmosdumotin as an Anticancer Agent: Homology Modeling, Docking and Molecular Dynamics Simulation Approach

Author(s): Changdev G. Gadhe, Gugan Kothandan and Seung Joo Cho

Volume 13, Issue 10, 2013

Page: [1636 - 1644] Pages: 9

DOI: 10.2174/18715206113139990302

Price: $65


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.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy