Carvacrol Derivatives as Antifungal Agents: Synthesis, Antimicrobial Activity and in Silico Studies on Carvacryl Esters

Chemical modifications of natural monoterpenoids to various derivatives have been reported to result in enhancement of biological activities when compared to parent compounds. In this context a well-known biocide and food additive, carvacrol, served as a basic scaffold onto which a phenolic functionality transformation by introducing acyl groups was performed. By using this simple methodology, we obtained a small series of 25 esters. For each of the obtained compounds we have performed structural characterization, in vitro antimicrobial testing and in silico calculation of physico-chemical, pharmacokinetic and toxicological properties. Despite numerous data on the synthesis and bioactivity of carvacryl ester lower homologues, there are scarce data on esters with acid components higher than C9, so that among 25 compounds, 10 were reported for the first time (spectral characterization for 12 are herein the first reported). Our research is also the first comprehensive study of carvacryl esters antifungal and of medium/long chain fatty acid esters antibacterial activities. Interesting result is that all the synthesized esters, regardless the nature of the R residue, have shown activity on fungal strain Aspergilus niger and on yeast Candida albicans comparable to carvacrol. Besides presented experimental data, implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties on the prepared compounds, may be valuable information in further research

The Effect of Camphor and Borneol on Rat Thymocyte Viability and Oxidative Stress

Camphor and borneol are wildly distributed in the essential oils of medicinal plants from various parts of the World. Our study has been carried out to evaluate the effect of these two bicyclic monoterpenes on rat thymocytes. Camphor and borneol at concentrations of 0.5 and 5 µg/mL did not induce significant toxicity on the immune system cells, while a significant increase of thymocyte viability was detected when cells were incubated with 50 µg/mL of camphor. A significant increase of cell viability was similarly detected when thymocytes were cultivated with borneol at concentrations of 0.5 and 5 µg/mL. The role of camphor and borneol in reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disturbances in rat thymocytes as well as their potential mechanism(s) of action were also discussed

The Effect of Camphor and Borneol on Rat Thymocyte Viability and Oxidative Stress

Camphor and borneol are wildly distributed in the essential oils of medicinal plants from various parts of the World. Our study has been carried out to evaluate the effect of these two bicyclic monoterpenes on rat thymocytes. Camphor and borneol at concentrations of 0.5 and 5 µg/mL did not induce significant toxicity on the immune system cells, while a significant increase of thymocyte viability was detected when cells were incubated with 50 µg/mL of camphor. A significant increase of cell viability was similarly detected when thymocytes were cultivated with borneol at concentrations of 0.5 and 5 µg/mL. The role of camphor and borneol in reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disturbances in rat thymocytes as well as their potential mechanism(s) of action were also discussed

Phenolic constituents of 17 Hypericum species from Turkey

OZEN, Tevfik/0000-0003-0133-5630WOS: 000254784200007

Effect of Hypogymnia physodes Extracts and their Depsidones on Micronucleus Distribution in Human Lymphocytes

Three lichen depsidones, physodalic acid (1), physodic acid (2), and 3-hydroxy physodic acid (3), were isolated from Hypogymnia physodes diethyl ether extract using column chromatography, and their structures determined by comparing their UV, H-1 and C-13 NMR spectroscopic and MS data with those given in the literature, as well as with data computed by CHEM draw ultra 11 software. The contents of 1, 2 and 3 were determined in the methanol (ME), acetone (AE), and diethyl ether (EE) extracts using reversed-phase high performance liquid chromatography with photodiode array detection. The extracts, isolated depsidones 1-3 and EE fraction F23 (consisting of 90% 2 and 3, in the ratio 5.5: 1) were evaluated for their in vitro effects on chromosome aberrations in peripheral human lymphocytes using the cytochalasin-B blocked micronucleus (CBMN) assay in doses of 1 mu g/mL and 2 mu g/mL of final culture solution. The frequency of MN was scored in binucleated cells, and nuclear proliferation index was calculated. It was found that 1, 2, 3, F23, and EE at 1.0 mu g/mL exerted a beneficial effect on lymphocyte cells giving a significant decrease of the frequency of MN in comparison with the positive control Amifostin WR-2721. Among the tested depsidones at a concentration of 1 mu g/mL, 3 exhibited the most prominent effect decreasing the frequency of MN by 30.3%, followed by 2 (28.2%) and 1 (22.0%). The extracts were less effective than the isolated depsidones

Effect of four lichen acids isolated from Hypogymnia physodes on viability of rat thymocytes

Four lichen acids, physodalic acid (F1), physodic acid (F2), 3-hydroxyphysodic acid (F3), and isophysodic acid (F4), were isolated from Hypogymnia physodes methanol extract using preparative reversed-phase high performance liquid chromatography and their structures were determined by UV, MS, H-1 NMR and C-13 NMR. This is the first report on the isolation of F4 from H. physodes. Isolated rat thymocytes were cultivated with increasing F1-F4 concentrations (0.1, 1, 10 mu g/well) and proliferative activity, viability, ROS (reactive oxygen species) production and MMP (mitochondrial membrane potential) disturbances were evaluated. Obtained results show significantly decreased thymocytes proliferation was observed when cells were treated with F1 (1 mu g, p LT 0.05; 10 mu g; p LT 0.001), F2 (10 mu g, p LT 0.05) and F3 compound (10 mu g, p LT 0.05). Significantly increased cytotoxicity was detected when cells were incubated with F1 (1 mu g, p LT 0.05; 10 mu g, p LT 0.01), F2 (10 mu g, p LT 0.05) and F3 compound (10 mu g, p LT 0.001). Increased H2DCF-DA fluorescence intensity, when cells were treated with F1 (1 mu g, p LT 0.001; 1 mu g, p LT 0.01; 10 mu g, p LT 0.001) and F2 (1 mu g, p LT 0.05; 10 mu g, p LT 0.01) compound, indicating the increase of intracellular ROS production. Simultaneously, increased ROS levels were followed with significantly decreased MMP when thymocytes were cultivated with F1 (0.1 mu g, p LT 0.001; 1 mu g, p LT 0.001; 10 mu g, p LT 0.001) and F2 compound (10 mu g, p LT 0.001). Thymocytes exposure to increased (0.1, 1, 10 mu g) concentrations of F3 and F4 compounds did not result with significant alterations in MMP and intracellular ROS production. We have shown that higher F1 and F2 concentrations induce thymocytes toxicity mainly through induction of oxidative stress, while cytotoxicity effect of F3 is followed with altered antioxidant/oxidant balance. The rigid 11H-dibenzo[b,e][1,4]dioxepin-11-one ring in the depsidone structure may play a important role for the examined biological activities