Molecular structures, chemical descriptors and pancreatic lipase (1LPB) inhibition by natural products: A DFT investigation and molecular docking prediction

Abstract

Abstract Density functional theory (DFT) calculations and molecular docking have been carried out on natural products containing eugenol, ginger, ascorbic acid, oleurpoein, piperine, hesperidin, quercetin, luteonil and curcumin in order to predict their biological activities and to analyse their pancreatic lipase inhibition. The biological activity predictions are based on the global and local chemical descriptors, namely, HOMO-LUMO gaps, chemical hardness, chemical potential, electrophilicity, dipole moment and Fukui functions. Our findings show that the studied compounds can be divided into two groups based on the chemical descriptors, one composed of those of low chemical descriptors, namely, eugenol, ginger, ascorbic acid and oleuropein and the second corresponds composed of piperine, hesperidin, quercetin, luteonil and curcumin in agreement with large HOMO-LUMO gaps and low electrophilicity for the former and conversely for the latter suggesting numerous and interesting biological activities. The frontier orbitals offer a deeper insight concerning the electron-donor and electron-acceptor capabilities, whereas, the local descriptors resulting from Fukui functions put emphasis on the active sites of different candidate ligands. The molecular docking was performed in order to compare and identify the inhibition activity of the natural candidate ligands against pancreatic lipase which were compared to that of synthesized ones. The molecular docking results revealed that the Luteonil compound has the best binding affinity of -8.56 kcal/mol due to their unique molecular structure and the position of -OH aromatic substituents.