Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists.
The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the r...
| Publicado en: | BioMed Research International Vol. 2017; pp. 1 - 19 |
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| Autores principales: | , , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
2/15/2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=121288723&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 121288723 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 2/15/2017 vid: 2017 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 121288723 121288723 121288723 10.1155/2017/3572394 121288723 ppf: 1 ppct: 18 formats: fmt: @attributes: type: P tig: atl: Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists. aug: au: Wang, Yuwei Han, Rui Zhang, Huimin Liu, Hongli Li, Jiazhong Liu, Huanxiang Gramatica, Paola affil: School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou 730000, China sug: subj: Virtual High-Throughput Screening Utilization Ligands Androgen Antagonists Italy Human Male Molecular Structure Prostatic Neoplasms Descriptive Statistics Funding Source Male ab: The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability. The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID_70128824, CID_70127147, and CID_70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide. In addition, molecular docking, molecular dynamics (MD) simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and AR. Through the analysis of the binding free energy and residue energy decomposition, we concluded that the newly discovered chemicals can in silico bind to AR with similar position and mechanism to the reported active compound and the van der Waals interaction is the main driving force during the binding process. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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