The effects of basil (Ocimum basilicum) and sage (Salvia officinalis) essential oils on selected virulence factors (biofilm formation, mature biofilm resistance, motility, and pyocyanin production) ...of Pseudomonas aeruginosa clinical isolates were evaluated in the present study for the first time. The two essential oils were chemically characterized by GC and GC-MS analyses. Linalool and (E)-anethole were found to be the main components of the investigated basil oil, while α-thujone and camphor were the major constituents of the studied sage essential oil. The oils inhibited biofilm formation up to 99.9% vs control, and significant reductions (74.7–99.9%) were also noted when the oils were applied to mature biofilms. Likewise, swimming, swarming, and twitching motility patterns were highly affected by both oils. The basil and sage oils reduced pyocyanin production by 13.32–55.6% and 5.0–58.7%, respectively. Thus, basil and sage essential oils are potentially highly efficient antipseudomonal agents that could be used against both acute and chronic infections.
•Basil and sage essential oils were chemically characterized and tested against P. aeruginosa.•Anti-biofilm experiments on P. aeruginosa isolates showed reductions up to 99.9%.•The oils eradicate all stages of biofilm development as well as mature biofilms.•The oils affected all motility types, and significantly reduced pyocyanin production.•Both essential oils are highly efficient anti-pseudomonal agents which decrease their virulence.
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•Pyrrolo3,4-cquinoline-1,3-diones were prepared by cyclization cascade reactions.•New class of potent hDHODH inhibitory demonstrated better activity than leflunomide.•Very low ...cytotoxicity against healthy HaCaT cells was observed.•The optimal lipophilicity was determined at physiological pH value.•The toxicological profile of the most active compounds was evaluated.
Twenty N-substituted pyrrolo3,4-cquinoline-1,3-diones 3a-t were synthesized by a cyclization reaction of Pfitzinger's quinoline ester precursor with the selected aromatic, heteroaromatic and aliphatic amines. The structures of all derivatives were confirmed by IR, 1H NMR, 13C NMR and HRMS spectra, while their purity was determined using HPLC techniques. Almost all compounds were identified as a new class ofpotent inhibitors against hDHODH among which 3a and 3t were the most active ones with the same IC50 values of 0.11 μM, about seven times better than reference drug leflunomide. These two derivatives also exhibited very low cytotoxic effects toward healthy HaCaT cells and the optimal lipophilic properties with logP value of 1.12 and 2.07 respectively, obtained experimentally at physiological pH. We further evaluated the comparative differences in toxicological impact of the three most active compounds 3a, 3n and 3t and reference drug leflunomide. The rats were divided into five groups and were treated intraperitoneally, control group (group I) with a single dose of leflunomide (20 mg/kg) group II and the other three groups, III, IV and V were treated with 3a, 3n and 3t (20 mg/kg bw) separately. The investigation was performed in liver, kidney and blood by examining serum biochemical parameters and parameters of oxidative stress.
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•ALC67 belongs to a recently discovered family of novel antiproliferative agents.•A synthetic library of optically pure ferrocenyl analogs of ALC67 was prepared.•Two compounds (6c-cis ...and 6-d) showed similar cytotoxicity to ALC67 and cisplatin.•The cytotoxicity depended on the electrophilicity of the N-acyl side chain group.•Derivative 6c-cis also manifested a selective anti-Bacillus cereus activity.
To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 μM, respectively, and IC50(HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 μM) and cisplatin (IC50(MRC5) = 4.0 μM and IC50(HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.
•Inula helenium essential oil was evaluated for anticandidal efficacy.•The oil showed high synergism with nystatin as well as potent anti-biofilm action.•All tested virulence factors of the strains ...were highly inhibited in contact with the oil.•The sorbitol and cholesterol experiments showed cell membrane-targeted action.•Results point to high applicative potential of this oil for the treatment of candidiasis.
Motivated by the ethnopharmacological application of Inula helenium, in the present study, the anticandidal potential of hydrodistilled root I. helenium essential oil was investigated by a microdilution method and the obtained minimal inhibitory concentrations (MICs) were further used to explore its synergistic potential. Additionally, the mode of action (sorbitol and cholesterol assays) and anti-virulence effects (anti-biofilm, germ-tube reducing and phospholipase-inhibitory activities) were also studied.
GC and GC/MS analyses showed that the isolated essential oil contained alantolactone and isoalantolactone as the dominant compounds (65.8 % and 25.5 %, respectively). The obtained MICs (0.009-0.312 mg/ml) varied for the strains generally demonstrating a medium-to-high anticandidal action. More importantly, the oil exhibited a high synergistic effect in combination with the antifungal agent nystatin. Experiments on the mode of action demonstrated that the oil affected the cell-membrane function. Considering virulence factors, the oil showed an antibiofilm activity, as well as a very high germ-tube reducing potential. The results demonstrated a complete inhibition of the enzyme phospholipase in the presence of the tested I. helenium root essential oil.
Based on the present results, I. helenium oil could be considered a natural agent that deserves to be further explored as a crop for the treatment of candididases.
The interest in the study of the gut microbiome has grown exponentially. Indeed, its impact on health and disease has been increasingly reported, and the importance of keeping gut microbiome ...homeostasis clearly highlighted. However, and despite many advances, there are still some gaps, as well as the real discernment on the contribution of some species falls far short of what is needed. Anyway, it is already more than a solid fact of its importance in maintaining health and preventing disease, as well as in the treatment of some pathologies. In this sense, and given the existence of some ambiguous opinions, the present review aims to discuss the importance of gut microbiome in homeostasis maintenance, and even the role of probiotics, prebiotics, and symbiotics in both health promotion and disease prevention.
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