Structure-based targeted molecular docking approach towards exploring the bioactive compounds of <i>Lagerstroemia speciosa</i> against black fungus (mucormycosis) and population pharmacokinetic simulation

Conventional treatments for Mucormycosis, a comorbidity in immune-compromised patients affecting the brain or respiratory tract, with medicines like posaconazole, isavuconazole, and amphotericin B possess concerning side effects. Hence, an alternative antifungal biocompound Ethyl 11-bromoundecanoate (EBD) from Lagerstroemia speciosa was investigated using in silico molecular docking against antigenic black fungus epitome. The interaction of EBD with two protein targets, 17 β-1,3-glucanosyltransferase (4WTP) and 1,3-β-glucanase (4M80) in black fungus revealed the docking scores of -4.83 and -6.70, respectively, while the positive control isavuconazole scored -8.49 and -9.94 against the respective proteins. Superior hydrogen bond interactions were demonstrated by EBD, despite lower binding affinity. By pharmacokinetic simulations, 5% oral bioavailability was predicted with a 43.13-hour maximum retention time. Rapid clearance (739.87 ml/min/kg) is caused by EBD’s high lipophilicity, which could be addressed by a hydrophilic delivery system. Better therapeutic efficiency at lower doses was indicated by population kinetics, and higher retention was observed in females compared to males. These findings suggest EBD as an alternative treatment for mucormycosis.