Integrative in silico and Petra/Osiris/Molinspiration (POM) analysis of baicalein: identification of therapeutically relevant pharmacophores against keloid pathology.

Abstract

Introduction: Keloid scars are a kind of skin disorder in which the scar grows beyond the boundaries of the original wound. Baicalein, a flavonoid, may treat keloids by targeting fibrosis, inflammation, and possible viral factors.

Methods: In silico studies were conducted to evaluate the potential anti-keloid effects of baicalein by predicting its interactions with three key proteins of the transforming growth factor-β (TGF-β) family (PDB IDs: 1VJY, 3TZM, and 7DV6). POM analysis was also used to understand the conditions that could enhance baicalein's efficacy.

Results: The results indicated that baicalein binds effectively to TGF-β family proteins via hydrogen bonds, showing strong affinities (1VJY: -9.9 kcal/mol, 3TZM and 7DV6: -9.3 kcal/mol), indicating its potential as a TGF-β receptor ligand. Osiris analysis gave a drug score of 75% for baicalein, while Molinspiration indicated good bioavailability with a cLogP of 2.84. Atomic charge distribution and pharmacophore site mapping through POM analysis indicate that baicalein exhibits an antiviral pharmacophoric moiety akin to known antiviral agents. This indicates that baicalein may act as a pro-drug, undergoing metabolic transformation to form a bis-bidentate ligand. Such ligands are crucial for forming bimetallic complexes that can function as efficient biocatalysts against various biological targets.

Conclusion: In-silico analysis suggests that baicalein may influence TGF-β receptors and exhibit anti-keloid activity. Additionally, POM analysis recommends that baicalein may serve as a lead compound with the potential to modulate TGF-β signalling and exhibit antiviral properties, indicating it as a dual-action agent against keloids and viral infections.