A convenient method for synthesis of Morita-Baylis-Hillman (MBH) 1,3-diene adducts and their in silico physicochemical, pharmacokinetics, and molecular docking evaluation studies

A series of Morita-Baylis-Hillman (MBH) 1,3-diene adducts are obtained according to a new, simple and practical method under mild operating conditions. Indeed, the action of t-BuOK on the cyclic allylic phosphonates of MBH in THF at room temperature leads to the corresponding 1,3-dienes with high stereoselectivity and good yields. The two Z and E isomers are determined by examining the NMR spectra which reveal, that the E configuration isomer is highly predominant. Density functional theory (DFT) computational analyses of compounds 3f and 3 g were performed to figure out the molecular structures and topologies of the predicted more energetic compounds, using the B3LYP functional and the 6-31 G(d,p) basis set. The HOMO- LUMO, and MEP analyses were visualized with the help of the Gaussview program. Multiwfn software is used for electron localization function (ELF) and localized orbital locator (LOL). We docked the synthesized compounds 3a-3g and 3 m into the protein binding sites of cyclooxygenase-1 (PDB ID: 3KK6) and cyclooxygenase-2 (PDB ID: 1CX2) to examine the binding mechanism, non-bonding interactions, and binding affinity of the tested compounds, using the molecular operating environment (MOE) 2015 program. Swiss ADME web tool is used to determine the physicochemical properties of the compounds: absorption, distribution, metabolism, elimination and toxicity (ADME), and drug-likeness characteristics.