Natural compounds from Ginkgo biloba L. targeting MPO, ERAP-2, DPP-4, PPAR-α, and ET B in cardiovascular diseases: Molecular docking and ADMET predictions

Abstract

Cardiovascular diseases stand as the foremost global cause of mortality. With most of the present-day drugs associated with serious side effects, the quest for safer interventions continues. Natural compounds from Ginkgo biloba L., an important Asian medicinal plant, were selected for investigations verifying their potential as new drug lead molecules against selected FDA-approved target proteins. A total of twenty-two compounds were analyzed against five targets: myeloperoxidase (MPO), endoplasmic reticulum aminopeptidase 2 (ERAP2), dipeptidyl peptidase-4 (DPP4), peroxisome proliferator-activated receptor α (PPARα), and endothelins (ET_B). Molecular docking was done using AutoDock Vina software package after the evaluation of physiochemical parameters. The binding energies were calculated from RASPD + and Vina, and correlation was calculated. For post-docking analysis, two programs (Pymol and Discovery Studio Biovia 2017) were applied. Pharmacokinetics and toxicity parameters were calculated using Swiss ADME, Admet SAR, Protox-II servers, and pkCSM. Eighteen compounds were found to exhibit 0/1 violations from Lipinski's rule of five. All these compounds exhibited high binding affinities for the selected target proteins, binding energies ranged from − 4.6 to -10.1 kcal/mol. Moderate to strong positive correlations were observed between energy values produced by RASPD + and VINA. Post-docking analysis further validated the strong binding affinities by revealing the number and nature of different atomic interactions. ADMET profiles also revealed the status of these compounds for good intestinal solubility in humans, oral bioavailability, inactive cytotoxicity, and liver toxicity. The analysis identified three compounds showing the highest affinity for the selected target proteins- bilobetin against MPO (-10.1) and DPP4 (-8.5); isoginkgetin against MPO (-10.0), ERAP2 (-8.7), PPARα (-10.1), and ET_B (-9.5); and sciadopitysin against DPP4 (-8.7), energies in kcal/mol. These three compounds also exhibited high GI values, a non-substrate status for P-gp, a non-inhibitory nature for CYP enzymes, a high lead-likeness score, and low toxicity, further validating the safety, selectivity, and effectiveness as potent drug lead molecules for treating CVDs and inflammation.