Multiclass comparative virtual screening to identify novel Hsp90 inhibitors: a therapeutic breast cancer drug target
| Autor: | Nageswara Rao Dunna, Srinivas Bandaru, Venkata Ravi Gutlapalli, Mukesh Yadav, Uday Raj Akare, Siddheshwar Rajadhyax, Anuraj Nayarisseri |
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| Rok vydání: | 2014 |
| Předmět: |
Indazoles
Pyridines Drug target Static Electricity Glycine Gene Expression Antineoplastic Agents Breast Neoplasms Pharmacology Anisoles Ligands Heterocyclic Compounds 2-Ring Catechin Structure-Activity Relationship User-Computer Interface Breast cancer Drug Discovery medicine Humans HSP90 Heat-Shock Proteins Virtual screening Binding Sites biology Chemistry Adenine Hydrogen Bonding General Medicine medicine.disease Hsp90 High-Throughput Screening Assays Molecular Docking Simulation Docking (molecular) Benzamides biology.protein Pyrazoles Female Hydrophobic and Hydrophilic Interactions PubChem Databases Chemical Protein Binding |
| Zdroj: | Current topics in medicinal chemistry. 15(1) |
| ISSN: | 1873-4294 |
| Popis: | Since the discovery of Hsp90, a decade ago, it has surfaced as a potential target in breast cancer therapy along with other cancers. In present study, we have selected seven established Hsp inhibitors viz., PU3, CCT-018159, CNF-2024, SNX-5422, NVP (AUY-922), EGCG and IPI-504 used in the treatment of cancer. Considering these seven inhibitors as a parent compound, ligand based search was carried out with 90% similarity in Pubchem database (31 million compounds). All the similar molecules belonging to respective parent compound along with similar compound were subjected to virtual screening using MolDock and PLP algorithm aided molecular docking. Compounds with highest docking rerank scores were selected and filtered through Lipinski’s drug-likeness filters and toxicity parameters. New candidate (Pubchem CID: 11363378) qualified to demonstrate considerable affinity towards Hsp90. The selected compound was further pharmcophorically incited for receptor- ligand interactions like H-bond, electrostatic, hydrophobic interactions etc. |
| Databáze: | OpenAIRE |
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