Anti-Staphylococcus aureus effectiveness of apigenin using in silico method combined with in vitro antibacterial activity analysis

Staphylococcus aureus is a bacterial pathogen that is resistant to multiple antibiotics, necessitating the development of alternative treatment approaches. Apigenin (APGN) has demonstrated antibacterial efficacy. This study aimed to evaluate the antibacterial efficacy of APGN against S. aureus compared with antibiotic s using in silico modeling and in vitro validation. Five important S. aureus targets, sortase A/B, penicillin-binding protein (PBP1b), the PASTA domain, and exotoxin (3URY), were explored via molecular docking and dynamics simulations. Interaction energy analysis and Molecular Mechanics / Poisson–Boltzmann Surface Area (MM-PBSA) were also calculated. Swiss Absorption, Distribution, Metabolism, and Excretion (SwissADME), Absorption, Distribution, Metabolism, Excretion, and Toxicity Laboratory, version 3.0 (ADMETLab 3.0), and System for Toxicity Prediction / System to Predict Acute Toxicity (STOP-Tox) were used to compare the pharmacokinetics and toxicity patterns of APGN and cefotaxime (CFTX). Zone diameter of inhibition (ZDI) was used to test the in vitro antibacterial efficacy against three clinical S. aureus strains (LMEM-2501, LMEM-2502, and LMEM-2503). APGN was administered alone and in combination with CFTX/ amikacin (AMKC) antibiotics. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were further determined, along with a 72-h biofilm inhibition study. APGN exhibited combinatorial synergy with conventional antibiotics, with ZDI values ranging from 7 mm to 25 mm. The MICs of APGN were determined to be 100 μg/ml, 175 μg/ml, and 150 μg/ml for the S. aureus target strains, respectively. Similarly, the MBCs of APGN were 125 μg/ml for LMEM-2501 and 175 μg/ml for LMEM-2502 and LMEM-2503. APGN demonstrated statistically significant, concentration-dependent antibiofilm efficacy of up to 80.77% against S. aureus . Although the current study demonstrates the antibacterial and biofilm-inhibitory efficacy of APGN against S. aureus, in vivo validation and clinical trials are warranted before APGN can be used as a prescription drug .