In Silico Evaluation of Chrysin: Pharmacokinetics, Toxicity, and Potential as an Adjuvant in Combating Vancomycin-Resistant Staphylococcus aureus

Abstract

Chrysin, a natural flavonoid found in honey and plants, has demonstrated antimicrobial properties and potential as an adjuvant to enhance antibiotic efficacy. This study evaluated the pharmacokinetics, toxicity, and efficacy of chrysin against Staphylococcus aureus infections, particularly Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Staphylococcus aureus (VRSA). Molecular docking was employed to assess chrysin’s interactions with D-Ala-D-Ala ligase (Ddl), an enzyme crucial for bacterial cell wall synthesis and vancomycin resistance. The docking analysis revealed a strong binding affinity of -8.6 kcal/mol, with key interactions such as hydrogen bonds and hydrophobic contacts enhancing the stability of the complex.

In addition to docking studies, chrysin’s absorption, distribution, metabolism, and excretion (ADME) properties were predicted using SwissADME. The results indicated high gastrointestinal absorption, moderate blood-brain barrier permeability, and low potential for cytochrome P450 enzyme inhibition, suggesting minimal drug-drug interaction risks.

These findings demonstrate that chrysin could effectively inhibit bacterial targets involved in vancomycin resistance, disrupt peptidoglycan synthesis, and enhance the efficacy of vancomycin against resistant S. aureus strains. Its favorable ADME profile and low toxicity further support its potential as a safe and effective antibiotic adjuvant. Future in vitro and in vivo studies are essential to validate these computational predictions and explore clinical applications of chrysin in managing resistant bacterial infections.