epi -Magnolin, a tetrahydrofurofuranoid lignan from the oleo-gum resin of Commiphora wightii , as inhibitor of pancreatic cancer cell proliferation, in-vitro and in-silico study.

Five known furofuran lignans, dia -sesamin ( 1 ), 5-methoxysesamin ( 2 ), epi -magnolin ( 3 ), kobusin ( 4 ) and yangambin ( 5 ) were isolated for the first-time from the oleo-gum resin of Commiphora wightii . This is the first report on the 13 C NMR assignments for epi -magnolin ( 3 ). Each of the isolated compounds was evaluated for its ability to inhibit MIA PaCa-2 pancreatic cancer cell line. Among them, epi -magnolin ( 3 ) displayed potential activity (IC 50 = 29 nM) compared to colchicine (IC 50 = 56 nM). 3D-flexible alignment revealed that epi -magnolin ( 3 ) has great matching with the tubulin polymerization inhibitor, colchicine. Meanwhile, docking studies exhibited that compounds 1 - 5 displayed good binding free energies against colchicine binding site (CBS) of tubulin with binding modes that were highly comparable to that of colchicine. Compounds 2 , 3 , and 5 showed superior binding free energies than colchicine (-24.37 kcal/mol). epi -Magnolin ( 3 ) showed the highest binding score against CBS. MD simulation studies confirmed the stability of epi -magnolin ( 3 ) in the active site for 200 ns. Furthermore, four online servers (Swiss ADME, pkCSM pharmacokinetics, AdmetSAR, and ProTox-II) were utilized to predict the ADMET parameters. The in-silico pharmacokinetics predictions reveled that epi -magnolin ( 3 ) has significant oral bioavailability and drug-like capabilities.Communicated by Ramaswamy H. Sarma.