Flavonoids as promising anticancer agents: an in silico investigation of ADMET, binding affinity by molecular docking...

Area of Science:

• Biochemistry
• Computational Chemistry
• Pharmacology

Background:

• Cancer remains a significant global health concern.
• Natural products, particularly flavonoids, are explored for anticancer properties.
• Tubulin is a validated target for anticancer drug development due to its role in mitosis.

Purpose of the Study:

• To evaluate the anticancer potential of flavonoids against tubulin using computational methods.
• To identify specific flavonoids with favorable drug-likeness and binding affinity to the tubulin colchicine site.
• To assess the stability of flavonoid-tubulin complexes through molecular dynamics simulations.

Main Methods:

• In silico analysis of ADMET properties for 104 flavonoids.
• Molecular docking of flavonoids to the colchicine binding site of Tubulin protein (PDB ID: 4O2B).
• 100 ns molecular dynamics simulations for top-scoring flavonoids to assess complex stability (RMSD, RMSF, rGy, SASA).

Main Results:

• Computational analysis identified promising flavonoid candidates with favorable ADMET profiles.
• Molecular docking revealed strong binding affinities of selected flavonoids to the tubulin colchicine site.
• Molecular dynamics simulations demonstrated stable interactions between the top flavonoids and tubulin.

Conclusions:

• Flavonoids exhibit significant potential as anti-tubulin agents for cancer therapy.
• This in silico study provides a strong basis for the development of novel flavonoid-based anticancer drugs.
• Computational approaches are valuable for identifying and optimizing natural product-based cancer therapeutics.