When Docking Predicts but Dynamics Dissociates: Understanding 7-O-Methylaloesinol’s Paradoxical Antibacterial Activity Through Integrated In Silco and In Vitro Approaches
Abstract
Loice Naswa Wechuli and Stephen S. Barasa
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major cause of global health crisis due to multidrug drug resistance thus being a major health threat calling for a new agent need for a novel of antimicrobial agents. Our previous molecular docking study identified several phytochemicals from Aloe barbadensis as potential inhibitors of MRSA targets. This study experimentally validates the excellent in vitro activity of 7-O-Methylaloesinol compound against S. aureus. 7-O-Methylaloesinol dissociated from FemA/FemB MRSA target during molecular dynamic simulation. Antibacterial activity against S. aureus ATCC 25923 was evaluated using the Kirby Bauer disk diffusion method. Gentamicin (10 μg/disk) was used as positive control, and DMSO as negative control. Zones of inhibition (ZOI) were measured in triplicate after 48 h incubation at 27°C. Data were analyzed using one way ANOVA with Tukey’s post hoc test. 7-O-Methylaloesinol produced the inhibition zone (38.7 ± 1.2 mm), significantly exceeding the positive control gentamicin (35.7 ± 4.0 mm, *p* < 0.05). While the negative control showed no zone of inhibition. This activity strongly correlated with docking scores (Spearman’s ρ = 0.87, *p* = 0.002). 7-O-Methylaloesinol demonstrate potent in vitro activity against S. aureus, with efficacy surpassing that of gentamicin under disk diffusion conditions. These results showing the high-water solubility- rapid diffusion of 7-O-Methylaloesinol in agar with disk diffusion zones reflecting disc diffusion rate and membrane effects not just binding affinity.