Abstract
The global prevalence of obesity reached approximately 15% in 2020 and is projected to rise to 18% by 2030, making the inhibition of pancreatic lipase activity to prevent the hydrolysis of triglycerides into free fatty acids and monoglycerides a crucial therapeutic strategy. This study aimed to analyze the root-mean-square deviation (RMSD), ∆GBinding, and amino acid interactions of 70 active compounds from neem (Azadirachta indica) leaves against the lipase enzyme via molecular docking, alongside designing a novel modified compound as an anti-obesity drug candidate. Structure preparation, geometric optimization, docking simulations, method validation, and interaction visualization were performed using ChemDraw, VegaZZ, PyRx-AutoDock Vina, PyMOL, and Discovery Studio, respectively. The docking results revealed that 67 of the 70 active compounds exhibited valid RMSD values of ≤ 2 Å, 67 compounds showed favorable binding energies ranging from ∆Gbinding -5.3 kcal.mol to -9.8 kcal/mol, and 22 compounds shared identical amino acid residue interactions with the positive control, orlistat. Furthermore, a novel modified derivative of chlorogenic acid, namely (E)-5-(2-carboxyvinyl)-2,3,4-trihydroxybenzoic acid, demonstrated an RMSD of 1.522 Å, ∆GBinding -7.1 kcal/mol, and a conserved SER A:176 interaction matching the orlistat control. In conclusion, these findings successfully identify both native active constituents from neem leaves and a newly modified analog as potent lipase inhibitors through molecular docking approaches.