Linking Antimicrobial Potential of Natural Products Derived from Aquatic Organisms and Microbes Involved in Alzheimer's Disease - A Review.

The following review is oriented towards microbes linked to Alzheimer's disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high-risk factors for AD occurrence.

Griseofulvin Derivatives: Synthesis, Molecular Docking and Biological Evaluation.

BACKGROUND: Griseofulvin - a mold metabolite produced by Penisilium griseofulvum is known as an antifungal drug. OBJECTIVE: Thus, the goal of this paper is the design and synthesis of new griseofulvin derivatives and evaluation of their antifungal activity. METHODS: Forty-two new compounds were synthesized using classical methods of organic synthesis and evaluated for their antimicrobial activity by microdilution method. RESULTS: All forty-two new compounds exhibited very good activity against eight tested micromycetes with MIC ranging from 0.0075-0.055 mg/ml and MFC from 0.02-024 mg/ml. All compounds exhibited better activity than reference drugs ketoconazole (7-42 times) and bifonazole (3-16 fold). The most promising was compound 15. The most sensitive fungal was found to be T. viride, while the most resistant, as was expected, was A. fumigatus. It should be mentioned that most of compounds exhibited better activity than griseofulvin. The molecular docking studies revealed that the most active compound have the same hydrophobic and H-bonding interactions with Thr276 residue observed for griseofulvin forming 3 hydrogen bonds while griseofulvin only one. In general, the molecular docking results coincide with experimental. CONCLUSION: Forty-two giseofulvin derivatives were designed, synthesized and evaluated for antimicrobial activity. These derivatives revealed good antifungal activity, better than reference drugs ketoconazole, bifonazole, and griseofulvin as well.

Could Flavonoids Compete with Synthetic Azoles in Diminishing Candida albicans Infections? A Comparative Review Based on In Vitro Studies.

Flavonoids are polyphenolic compounds with already confirmed various health benefits. This review will shed light on flavonoids as potential antifungals in Candida albicans infections. C. albicans is an opportunistic pathogen able to cause serious health issues due to numerous virulence factors amplifying its pathogenicity. One of the most important virulence factors is Candida ability to form biofilms which are highly resistant to the treatment of antifungal drugs; making diminishing of this pathogen even more challenging. This review will focus on current knowledge on individual flavonoid compounds having the potential to deal with C. albicans in vitro, with special turn on antibiofilm potential and insight into the mode of action, where available. Majority of the commercial drugs for the treatment of candidiasis belong to azole class, so the activity of flavonoids will be compared with the activity of newly synthetized azole compounds, as well as with azole drugs that are already on the market as official therapeutics. This literature review will provide pros and cons for pushing future research towards exploring novel synthetic azoles or further examination of a wide pallet of natural flavonoids.

Characterization of phenolic compounds in tincture of edible Nepeta nuda: development of antimicrobial mouthwash.

The activity of edible Nepeta nuda L. (Lamiaceae) tincture and Listerine towards a selected group of oral pathogenic microorganisms (4 bacterial and 9 fungal strains) has been explored. Their potentials to inhibit the formation of biofilm and to diminish established biofilm have been compared. The amount of N. nuda tincture and swishing time necessary for reaching better or equivalent antimicrobial effect than that of Listerine have been predicted. Phenolic compounds in N. nuda tincture are determined by LC-DAD/ESI-MSn. Both Listerine and N. nuda tincture possess good antimicrobial potentials (MIC in the range of 0.8-15 µL per well) including inhibition of biofilms. Rosmarinic acid and verminoside are the most dominant phenolic compounds present in the N. nuda tincture. Based on in vitro results, we infer that it is more desirable to swish 20 mL of mouthwashes (Listerine and N. nuda tincture, 100 mg mL-1) for 30 s when dealing with selected microorganisms in general and for 60 s (N. nuda tincture) when dealing with bacterial biofilms.

Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors.

Four heteroaromatic compounds bearing nitrate esters were selected using a virtual-screening procedure as putative sterol 14α-demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR spectroscopy studies, in silico docking, and molecular dynamics simulations were used to investigate further the selectivity of these compounds to fungal CYP51. All compounds exhibited good antimicrobial properties, indicated with low minimal inhibitory concentrations and ability to inhibit formation of fungal biofilm. Moreover, all of the compounds had the ability to inhibit growth of C. albicans cells. N-(2-Nitrooxyethyl)-1Η-indole-2-carboxamide was the only compound with selectivity on C. albicans CYP51 that did not exhibit cytotoxic effect on cells isolated from liver and should be further investigated for selective application in new leads for the treatment of candidiasis.

Chemical composition and bioactive properties of the wild mushroom Polyporus squamosus (Huds.) Fr: a study with samples from Romania.

In Eastern Europe, wild mushrooms are widely collected in mountain areas and used for their medicinal properties or as healthy foods. This study aimed at determining the chemical composition (nutritional value, free sugars, organic acids, phenolic compounds, fatty acids and tocopherols) and bioactive properties (antioxidant, antimicrobial and antiquorum sensing) of wild Polyporus squamosus (Huds.) Fr from Romania. The results indicate that the fruiting bodies of P. squamosus are rich in carbohydrates (74.22 g per 100 g dw) and proteins (18.7 g per 100 g dw). Trehalose was the main free sugar, while malic acid was the organic acid detected in the highest amount (2.21 g per 100 g dw), and p-hydroxybenzoic acid was the main phenolic compound. Among tocopherols, ß-tocopherol was the most abundant form (114.7 µg per 100 g dw). Additionally, regarding the fatty acids' pattern, polyunsaturated acids represent more than 57% of all fatty acids, followed by monounsaturated fatty acids (24.96%). The highest measured antioxidant effect of P. squamosus extract was found using the TBARS inhibition assay (EC50 = 0.22 mg mL-1), followed by the ß-carotene/linoleate assay (EC50 = 1.41 mg mL-1). A minimal inhibitory concentration of the tested extracts was obtained between 0.61-20.4 mg mL-1, while the bactericidal effect was achieved between 1.2-40.8 mg mL-1. Antibiofilm potential was obtained at all tested concentrations, and subinhibitory concentrations of the extract exhibited an antiquorum effect and reduced the formation of P. aeruginosa pili, which all together influenced the virulence of this bacterium. Due to the investigated bioactivities and compounds of P. squamosus and its well-balanced nutritional profile, this mushroom can be further used as a medicinal ingredient based on its antioxidative and antimicrobial potential.

Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions.

Bioactive potential of apigenin derivative apigenin-7-O-glucoside related to its antifungal activity on Candida spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of Candida spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 C. albicans enzyme. Cytotoxic potential of apigenin-7-O-glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7-O-glucoside towards all Candida isolates. Breakdown of C. albicans plasma membrane was achieved upon treatment with apigenin-7-O-glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to C. albicans CYP51 protein. Besides, apigenin-7-O-glucoside was more effective compared to apigenin in reduction of cell's viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7-O-glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7-O-glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7-O-glucoside has more potent activity compared to apigenin in all assays that we used.

Chemical, nutritive composition and a wide range of bioactive properties of honey mushroom Armillaria mellea (Vahl: Fr.) Kummer.

A. mellea fruiting bodies collected from nature were chemically characterized and shown to be rich in carbohydrates (81.25 g per 100 g dw), ash, fat and proteins (8.84 g per 100 g dw, 1.97 g per 100 g dw and 1.81 g per 100 g dw, respectively). Mannitol was the main free sugar while malic acid was the most abundant organic acid. δ-Tocopherol was the dominant form of tocopherols with 42.41 µg per 100 g dw. Polyunsaturated fatty acids were predominant, followed by saturated and monounsaturated fatty acids. A methanolic extract prepared from these samples was tested for antioxidant, quorum sensing and antimicrobial assays, as well as for its cytotoxicity effects. The extract showed antimicrobial activity against all tested microorganisms, including Candida albicans. Furthermore, when tested at sub-MIC concentration, it showed reduction of virulence factors and biofilm formation against Pseudomonas aeruginosa. The extract also exhibited antioxidant activity and did not show toxicity against tumor and non-tumor cells. Due to the observed bioactive properties and compounds of the honey mushroom and its well-balanced nutrients, this mushroom emerges as an interesting functional food and a source of nutraceuticals with applications in different diseases based on antioxidant and antimicrobial effects.

Sensitivity of clinical isolates of Candida to essential oils from Burseraceae family.

The aim of this study was to investigate the chemical composition and antifungal activity of four commercial essential oils from the Burseraceae family - two Boswellia carterii Flueck oils, Canarium luzonicum (Blume) A. Gray oil, and Commiphora myrrha (Nees) Engl oil, against most common Candida spp. recovered from the human oral cavity. The essential oil samples were analyzed by GC-FID and GC/MS. The analysis showed that major essential oils' components were α-pinene (23.04 % and 31.84 %), limonene (45.62 %) and curzerene (34.65 %), respectively. Minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations were determined using a microdilution standardized technique. All tested Candida spp. clinical isolates and ATCC strains showed susceptibility to tested essential oils in a dose dependent manner. The strongest antifungal activity was shown by essential oil of B. carterii, sample 2; the average MIC values ranged from 1.25 to 1.34 mg/ml, and MFC values ranged from 2.50 to 3.75 mg/ml, depending on the fungus. This study supports the possible use of essential oils from the Bursecaceae family in reduction and elimination of Candida spp. populations in patients with oral cavity fungal infections.

Could essential oils of green and black pepper be used as food preservatives?

Black and green pepper essential oils were used in this study in order to determine the chemical composition, in vitro antimicrobial activity against food spoilage microorganisms and in situ oils effect on food microorganism, after incorporation in chicken soup, by suggested methodology for calculation of Growth inhibition concentrations (GIC50). Chemical analysis revealed a total of 34 components. The major constituent of black pepper oil was trans-caryophyllene (30.33 %), followed by limonene (12.12 %), while ß-pinene (24.42 %), δ(3)-carene (19.72 %), limonene (18.73 %) and α-pinene (10.39 %) were dominant compounds in green pepper oil. Antimicrobial activity was determined by microdilution technique and minimal inhibitory (MIC) and minimal bactericidal/fungicidal concentrations (MBC/MFC) were determined. Green pepper oil showed stronger antibacterial and antifungal activity (MIC 0.50-1.87; MBC 0.63-2.5 mg/ml; MIC 0.07-0.16; MFC 0.13-1.25 mg/ml) against black pepper oil (MIC 0.07-3.75; MBC 0.60-10.00 mg/ml; MIC 0.63-5.00; MFC 1.25-10.00 mg/ml. Oils successfully inhibited the growth of S. aureus in chicken soup in a dose dependent manner. GIC50 values were calculated after 24, 48 and 72 h and were in range of 0.156-0.689 mg/ml. The 50 % inhibitory concentrations (IC50) of EOs were 36.84 and 38.77 mg/ml with in 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay respectively. The obtained results revealed that black and green pepper volatiles are efficient in controlling the growth of known food-spoilage microorganisms.