Quercetin-3'-O-glucoside and delphinidin-3-O-sambubioside from Hibiscus sabdariffa Linn.: A molecular docking study against pathogen-associated molecular patterns and Toll-like receptors

Context: Roselle (Hibiscus sabdariffa L.) contains flavonoids such as quercetin-3'-O-glucoside and delphinidin-3-O-sambubioside, which have potential antibacterial and immunomodulatory properties, and may act as an antibacterial, antioxidant, and anti-inflammatory agent. Molecular docking simulations were employed to study the binding affinity of the compounds with bacterial pathogen-associated molecular patterns (PAMPs), peptidoglycan, flagellin, dectin, and lipopolysaccharides (LPS) and with immune-related Toll-like receptors (TLRs) (TLR-1, TLR-2, TLR-4, and TLR-6). A dual mode of action, involving the inhibition of bacterial virulence and the induction of the host immune response, suggests that these compounds are promising drug candidates against multidrug-resistant bacterial infections. Aims: To investigate the molecular docking interactions of quercetin-3'-O-glucoside, delphinidin-3-O-sambubioside, and cyanidin-3-O-sambubioside from H. sabdariffa with peptidoglycan, flagellin, dectin, LPS, and TLRs (TLR-1, TLR-2, TLR-4, and TLR-6). Methods: Ligand data were retrieved from PubChem and docked to PAMPs (peptidoglycan, flagellin, dectin, LPS) and TLRs (TLR-1, -2, -4, -6). absorption, distribution, metabolism, excretion, and toxicity profiling were conducted via SwissADME and ProTox. Results: Quercetin-3'-O-glucoside and delphinidin-3-O-sambubioside showed the most favorable binding affinities and low toxicity, outperforming standard antibiotics in docking affinity. These compounds have shown promise as immunomodulators, given their strong negative binding with key TLRs and their efficient inhibition of bacterial PAMPs, including LPS and flagellin. These active compounds are suggested for adjunctive treatment of Gram-negative bacterial infections. Conclusions: These flavonoids may serve as potential therapeutic candidates due to their dual action abilities, which interfere with bacterial virulence factors and modulate the host immune response.