An efficient synthesis of 4H-chromene-4-ones via enamino ketones, with cyclization by using T3P^® under microwave heating is described. This is the first report for the synthesis of chromones by using T3P^®. Significant features of this method include short reaction times and high-purity products.

The work presents a library of piperine derivatives as potential inhibitors of the main protease protein (Mpro) functionality using Docking Studies, Molecular Dynamics (MD) Simulations and Absolute Binding Free-Energy calculations. 342 ligands were selected for this work and docked with Mpro protein. Among all the ligands studied, PIPC270, PIPC299, PIPC252, PIPC63, PIPC311 were the top five docked conformations having significant hydrogen bonding and hydrophobic interactions inside the active pocket of Mpro. These top five ligands were subjected to MD simulations for 100 ns using GROMACS. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA) and hydrogen bond analysis revealed that the ligands bounded to protein remain stable without significant deviations during the course of MD simulations. Absolute binding free energy (ΔG_b) was calculated for theses complexes and found that the ligand PIPC299 shows the prevalent binding affinity with binding free-energy of about −113.05 Kcal/mol. Thus, these molecules can be further tested by in vitro and in vivo studies on Mpro. This study lays a path to explore the new functionality of piperine derivatives as novel drug like molecules. Communicated by Ramaswamy H. Sarma

Phospholipase A2 (PLA2), Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are arachidonic acid metabolizing enzymes and their inhibitors have been developed as therapeutic molecules for cancer and inflammation related disorders. In the present study, PLA2, COX 1&2 and 5-LOX inhibitory studies of Borassus flabellifer seed coat extract were carried out and substantial 5-LOX inhibitory activity was found. Dammarane triterpenoid 1 (Dammara-20,23-diene-3,25-diol) was isolated according to 5-LOX activity guided isolation, and screened for COX (1 & 2) inhibitory activities. Dammarane triterpenoid 1 inhibited carrageenan-induced rat paw edema and TNF-α secretion levels in lipopolysaccharide (LPS)-induced THP-1 human monocytes. Anticancer activity studies demonstrated the antiproliferative effect of dammarane triterpenoid 1 on various cancer cell lines including MIA PaCa-2 pancreatic, DU145 prostate, HL-60 leukemia and Caco-2 colon cancers. Dammarane triterpenoid 1 showed good antiproliferative activity on MIA PaCa-2 pancreatic cancer cell line with IC₅₀ of 12.36±0.33 µM, among other tested cell lines. Apoptosis inducing activity of dammarane triterpenoid 1 was confirmed based on increased sub-G0 phase cell population in cell cycle analysis, loss of mitochondrian membrane potential, elevated levels of cytochrome c, nuclear morphological changes and DNA fragmentation in MIA PaCa-2 pancreatic cancer cells. Therefore, dammarane triterpenoid skeleton may raise the hope of developing novel anti-inflammatory and anticancer drugs in the future.