Elucidating the ACE inhibitory properties of the novel compounds of the pine needle aqueous extracts using in silico docking studies

A plentiful and underutilized source of bioactive phytocompounds with great therapeutic potential is pine needles (Pinus roxburghii). The current study employs a molecular docking approach to examine the angiotensin-converting enzyme (ACE) inhibitory activity of five novel compounds observed in the aqueous extract of the pine needles, viz. Embelin, synthetic Pyrrolo[3,4-c]pyrazole derivative, DL-Carbidopa, Thymidine, D-pantothenic acid, using lisinopril as the reference standard. The in-silico docking was used to assess the binding affinity and interaction patterns of phytocompounds obtained through prior chromatographic profiling inside the ACE active site. According to the docking results, a number of compounds showed strong binding affinities, with docking scores (-5.686 kcal/mol, -9.046 kcal/mol, -8.217 kcal/mol, -7.049 kcal/mol, -6.741 kcal/mol) that were either equal to or higher than those of lisinopril (-6.755 kcal/mol), suggesting a considerable inhibitory potential. Effective ACE activity inhibition and ligand enzyme complex stability depend on these interactions. Additionally, there was a significant overlap between the binding conformations of the best-performing phytocompounds and lisinopril, indicating a comparable mechanism of inhibition. Enhanced binding interactions were greatly aided by the presence of functional groups like hydroxyl and carbonyl moieties. In general, the results indicate the potential of phytochemicals derived from pine needles as natural ACE inhibitors and offer a robust scientific basis for further in vitro and in vivo validation toward the formulation of plant-based hypertension therapies.