No abstract

Resveratrol is a natural polyphenol found mainly on red grapes and in red wine, pointed as an important anti-inflammatory/immunomodulatory molecule. However, its bioavailability problems have limited its use encouraging the search for new alternatives agents. Thus, in this study, we synthetize 12 resveratrol analogues (6 imines, 1 thioimine and 5 hydrazones) and investigated its cytotoxicity, antioxidant activity and in vitro anti-inflammatory/immunomodulatory properties. The most promising compounds were also evaluated in vivo. The results showed that imines presented less cytotoxicity, were more effective than resveratrol on DPPH scavenger and exhibited an anti-inflammatory profile. Among them, the imines with a radical in the para position, on the ring B, not engaged in an intramolecular hydrogen-interaction, showed more prominent anti-inflammatory activity modulating, in vivo, the edema formation, the inflammatory infiltration and cytokine levels. An immunomodulatory activity also was observed in these molecules. Thus, our results suggest that imines with these characteristics presents potential to control inflammatory disorders.

Vernonia polyanthes is a medicinal plant used to treat many disorders, including infectious diseases. This study investigated the chemical constituents and the antibacterial activity of V. polyanthes leaf rinse extract (Vp-LRE). The chemical characterization of Vp-LRE was established using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS), and glaucolide A was identified through 1H and 13C nuclear magnetic resonance (NMR) and mass fragmentation. The cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The antibacterial activity was assessed by minimal inhibitory concentration and minimal bactericidal concentration. Interactions between ligands and beta-lactamase were evaluated via molecular docking. UHPLC/Q-TOF-MS detected acacetin, apigenin, chrysoeriol, isorhamnetin, isorhamnetin isomer, kaempferide, 3′,4′-dimethoxyluteolin, 3,7-dimethoxy-5,3′,4′-trihydroxyflavone, piptocarphin A and glaucolide A. Vp-LRE (30 µg/mL) and glaucolide A (10 and 20 μg/mL) were cytotoxic against RAW 264.7 cells. Glaucolide A was not active, but Vp-LRE inhibited the Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Salmonella Choleraesuis and Typhimurium, with a bacteriostatic effect. The compounds (glaucolide A, 3′,4′-dimethoxyluteolin, acacetin and apigenin) were able to interact with beta-lactamase, mainly through hydrogen bonding, with free energy between −6.2 to −7.5 kcal/mol. These results indicate that V. polyanthes is a potential natural source of phytochemicals with a significant antibiotic effect against MRSA strains.