Docking-Based Virtual Screening Method for Selecting Natural Compounds with Synergistic Inhibitory Effects Against...

Area of Science:

• Computational drug discovery
• Natural product chemistry
• Cancer biology

Background:

• Cancer development involves complex signaling pathways.
• Identifying natural compounds with synergistic effects is crucial for multi-targeted cancer therapy.
• Existing methods may not fully capture the synergistic potential of natural compounds.

Purpose of the Study:

• To develop a methodology for identifying medicinal plants containing natural compounds with synergistic anti-cancer effects.
• To screen for compounds that can inhibit cancer survival and proliferation via multi-targeted mechanisms.
• To identify potential plant sources for these synergistic compounds.

Main Methods:

• Defined cancer signaling pathways using KEGG database.
• Investigated protein-protein interactions (PPIs) using STRING software to identify 14 key protein targets.
• Filtered natural compounds based on IC50 values from the NPASS database.
• Performed molecular docking of 1,107 natural compounds against selected cancer and side-effect targets.

Main Results:

• Identified 14 hub proteins with high interaction degrees as key targets.
• Selected natural compounds with IC50 < 20000 nM for docking.
• Identified compounds with low binding energy to selected targets as potential synergistic inhibitors.
• Highlighted plants with a wide range of identified compounds as promising sources.

Conclusions:

• Proposed a pre-screening methodology for natural compounds with synergistic anti-cancer potential.
• The methodology aids in identifying compounds targeting multiple molecular mechanisms in cancer.
• Further experimental validation is required to confirm the efficacy of identified compounds.