Phenological and Environmental Factors' Impact on Secondary Metabolites in Medicinal Plant Cotinus coggygria Scop.

Cotinus coggygria Scop. (smoketree) is a phytotherapeutically valuable shrub growing in specific areas in many Eurasian countries. Exploring the intrinsic and extrinsic (abiotic) factors that modulate its secondary metabolism has fundamental and applicative importance. Three smoketree plants from the same population were studied for a period of 4.5 months. Their extracts were characterized using LC-MS/MS, HPLC-UV-VIS-DAD and colorimetric assays to determine the chemical composition and antioxidant potential. Multivariate analysis was applied to correlate the metabolomic data with registered habitat variables and phenological stages. The identified and quantified compounds belonged to the flavonoids (myricetin-3-O-galactoside, myricitrin) and hydrolysable tannins groups (pentagalloyl glucose, methyl gallate, methyl digallate I). Phenolic compounds and tannins were synthesized abundantly in the flowering and fruit stages, whereas flavonoids and triterpenes accumulated during senescence. The antioxidant activities varied between detection methods, samplings and individuals and were only punctually correlated with the compound contents in certain phenological stages. Based on the HCAbp analysis, the samples clustered under four groups, according to their metabolic profile. The CCA analysis revealed that during the reproductive stages (flower, fruit or seed), the secondary metabolism of the plants' leaves is sensitive to the action of abiotic factors, while in senescence, the metabolic content is according to the phenological phase. This study provides a first attempt at understanding the interplay between the habitat and the metabolome of smoketree.

Synthesis and Biological Evaluation of New N-Acyl-α-amino Ketones and 1,3-Oxazoles Derivatives.

In order to develop novel bioactive substances with potent activities, some new valine-derived compounds incorporating a 4-(phenylsulfonyl)phenyl fragment, namely, acyclic precursors from N-acyl-α-amino acids and N-acyl-α-amino ketones classes, and heterocycles from the large family of 1,3-oxazole-based compounds, were synthesized. The structures of the new compounds were established using elemental analysis and spectral (UV-Vis, FT-IR, MS, NMR) data, and their purity was checked by reversed-phase HPLC. The newly synthesized compounds were evaluated for their antimicrobial and antibiofilm activities, for toxicity on D. magna, and by in silico studies regarding their potential mechanism of action and toxicity. The 2-aza-3-isopropyl-1-[4-(phenylsulfonyl)phenyl]-1,4-butanedione 4b bearing a p-tolyl group in 4-position exhibited the best antibacterial activity against the planktonic growth of both Gram-positive and Gram-negative strains, while the N-acyl-α-amino acid 2 and 1,3-oxazol-5(4H)-one 3 inhibited the Enterococcus faecium biofilms. Despite not all newly synthesized compounds showing significant biological activity, the general scaffold allows several future optimizations for obtaining better novel antimicrobial agents by the introduction of various substituents on the phenyl moiety at position 5 of the 1,3-oxazole nucleus.