New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenase (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds. Prediction of biological activity was performed by PASS, and prediction results were analyzed with PharmaExpert software. Nine 2-(thiazole-2-ylamino)-5-phenylidene-4-thiazolidinone derivatives differing by the phenyl group substitution were selected for synthesis and experimental testing as potential COX/LOX inhibitors. Eight tested compounds exhibited anti-inflammatory activity in the carrageenin-induced paw edema. It was shown that seven tested compounds (77.8%) were LOX inhibitors, seven compounds were COX inhibitors (77.8%), and six tested compounds (66.7%) were dual COX/LOX inhibitors. Analysis of lipophilicity of the compounds showed a negative correlation with inhibition of edema formation. The binding modes of the most active compounds of this series (2-(thiazole-2-ylamino)-5-( m-chlorophenylidene)-4-thiazolidinone for COX-1 and COX-2, and 2-(thiazole-2-ylamino)-5-( m-nitrophenylidene)-4-thiazolidinone for 15-LOX) were proposed on the basis of docking studies.

Chemical investigation of ethyl acetate extract from the aerial parts of Helleborus cyclophyllus (A. Braun) Boiss. led to the isolation of ten natural products, and their structures were identified to be: 2-deoxy-D-ribono-1,4-lactone (1), 2-O-feruloyl-L-malate (2), three flavonoids: quercetin 3-O-β-D-galactopyranoside (3), quercetin 3-O-6′′-(3-hydroxy-3methyl-gloutaryl)-β-D-glucopyranoside (4) and quercetin 3-O-(2‴-caffeoylsophoroside) (5), 6-O-caffeoyl-1-O-p-coumaroyl-β-D-glucopyranoside (6), two ecdysteroids: 20hydroxyecdysone (7) and polypodine B (8) and two bufadienolides: deglucohellebrin (9) and hellebrin (10), on the basis of MS and NMR spectra. This is the first report on the occurrence of compounds (2)-(6) in the genus Helleborus. The chemotaxonomic significance of these compounds was summarised. Bioactivity score, molecular and pharmacokinetic properties of the isolated compounds were calculated by online computer software program Molinspiration. Compounds showed promising bioactivity scores for drug targets. Moreover, some of the isolated phenolic compounds were tested for their antioxidant and antiinflammatory activities. Tested compounds present antioxidant ability correlated to the presence of the phenolic hydroxyl groups.