Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies.

In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 - 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ±â€¯1.5 µM and 12.1 ±â€¯1.5 µM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single-crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.

Crystal structure and Hirshfeld surface analysis of 3-(3-hy-droxy-phen-yl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one hemihydrate.

High-quality single crystals of the title compound, 2C13H11NO2·H2O, were grown and a structural analysis was performed. The asymmetric unit comprises one mol-ecule of 3-(3-hy-droxy-phen-yl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP), which was recently discovered to be a promising anti-MRSA candidate, and a half-mol-ecule of water. The compound crystallizes in the monoclinic space group P2/c. The crystal structure features inter-molecular pyrrole-N-H⋯O (water), carbon-yl/keto-C-O⋯H-O-phenol and phenol-C-O⋯H (water) hydrogen bonds, which help to consolidate the crystal packing. A Hirshfeld surface analysis for the components in the asymmetric unit showed that H⋯H (40.9%) and H⋯C/C⋯H (32.4%) contacts make the largest contributions to the inter-molecular inter-actions of 3HPPP. Considering the presence of water, in its vicinity H⋯O/O⋯H and H⋯C/C⋯H are the most significant contacts, contributing 48.7 and 29.8%, respectively.