Isolation of phytoconstituents from an extract of Murraya paniculata with cytotoxicity and antioxidant activities and in silico evaluation of their potential to bind to aldose reductase (AKR1B1).

The study on Murraya paniculata (Orange Jasmine) stem bark extract found it to have antioxidant and cytotoxic proper-ties. The structures of the isolated phytoconstituents were determined using NMR spectroscopy. Compounds were evaluated for their potential to be aldose reductase inhibitors using molecular docking and dynamics (MD) simulations. Phytochemical screening of methanolic crude extract was performed from which different fractions of the extract were screened for antioxidant activity using the DPPH radical scavenging method and cytotoxicity using the brine shrimp lethality bioassay. The aqueous fraction showed strong antioxidant activity as compared to the standard butylated hy-droxytoluene, whereas pet ether, dichloromethane, chloroform and methanolic extract exhibited moderate antioxidant activity. Activities in the DPPH assay ranged from 17 to 63 µg/ml and all fractions showed cytotoxic activity. Five identified phytochemical compounds (1-5) include ergosterol endoperoxide (1), the coumarin derivatives 7-methoxy-8-(3-methylbut-2-enyl)-1-benzopyran-2-one (2) and 5,7-dimethoxy-8-(3-methylbut-2-enyl)-1-benzopyran-2-one (3) and a mixture of β-sitosterol (4), and stigmasterol (5). Among them ergosterol endoperoxide has been isolated from the stem bark of the M. paniculata for the first time. MD simulations of the identified compounds indicated their potential to bind to the aldose reductase (AKR1B1) protein. Predicted binding affinities of the compounds based on the site identification the ligand competitive saturation (SILCS) technology was -15.04, -8.85, -9.83, -11.95, and -11.75 kcal/mol for 1 through 5, respectively. The present results are anticipated to lead to further study of the activities of the five compounds including experimental evaluation of their inter-actions with AKR1B1.