Study of Peptidic HIV-1 Protease Inhibitors Based on Pharmacokinetics, Site Selectivity, Intermolecular Interaction and Energy Parameters

Protease inhibitors (PIs) remain a feasible option for the therapy of people living with HIV, particularly in complex clinical and virological circumstances. Nonetheless, they are linked to increased metabolic toxicity and drug-drug interactions, compared to newer drugs in this class. A comparative study of 51 HIV-1 protease inhibitors from the peptidic group was conducted, focusing on pharmacokinetic properties, site selectivity parameters, intermolecular interactions, and energy parameters to analyze their chemical-biological interactions, potentially offering strategies to enhance the development of superior anti-HIV medications within this category. The logarithms of the reciprocal of IC50 for the compounds mentioned above have been utilized as the biological endpoint (log1/C) in this research. The 3D modeling and minimum energy of all fifty-one compounds were obtained using CAChe 0.5 by opting for parametric model 3. All the regression equations were developed using Project Leader software, and statistical work was executed using Statistica 0.2. Research indicates that the optimal model is developed through pharmacokinetic properties. This further demonstrates that these characteristics (molecular weight and hydrogen bond acceptor) are essential for defining the pharmacokinetics of the medications. The findings from this study indicate that these terms can serve as indicators of biological activity, and the study will help to modify the existing HIV protease inhibitors into the required activity with minimal or no side effects.