Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors...

Area of Science:

• Computational chemistry
• Pharmacoinformatics
• Oncology

Background:

• Breast cancer involves uncontrolled cell growth driven by overexpressed genes.
• Targeting heat shock protein 90 (HSP90) and growth factor receptors like EGFR and HER2/neu is a key strategy in breast cancer chemoprevention.
• Identifying effective inhibitors is crucial for developing novel chemopreventive agents.

Purpose of the Study:

• To identify potential drug candidates for breast cancer using a pharmacoinformatic approach.
• To screen compounds targeting HSP90, EGFR, and HER2/neu receptors, which are overexpressed in breast cancer.
• To evaluate the drug-likeness and binding affinities of potential lead compounds.

Main Methods:

• In silico screening and pharmacoinformatic analysis were employed.
• Drug-likeness filters were used to assess the pharmacological activity of compounds.
• Molecular docking and energy minimization (Amber ff12SB force field) were performed to analyze binding interactions.

Main Results:

• Five chemical compounds (S-258282355, S-258012947, S-259417539, S-258002927, S-259411474) exhibited high binding energies (-8.7 to -10.3 kcal/mol).
• These compounds showed multi-targeted activity against HSP90, EGFR, and HER2/neu.
• The identified compounds demonstrated favorable ADMET profiles and cytochrome P inhibitory activity.

Conclusions:

• The five identified compounds show significant potential as multi-targeted anticancer agents for breast cancer treatment.
• These compounds possess favorable drug-like properties, suggesting their viability for future drug development.
• Further research is warranted to develop these promising hits into novel chemopreventive drugs for breast cancer.