Light conditions affect the growth, chemical composition, antioxidant and antimicrobial activities of the white-rot fungus Lentinus crinitus mycelial biomass.

The mycelial biomass of basidiomycetes is a promising source of compounds and represents an alternative for industrial and biotechnological applications. Fungi use light as information and hold photoresponse mechanisms, in which sensors respond to light wavelengths and regulate various biological processes. Therefore, this study aimed to investigate the effects of blue, green, and red lights on the growth, chemical composition, and antioxidant and antimicrobial activity of Lentinus crinitus mycelial biomass. The chemical composition of the mycelial biomass was determined by chromatographic methods, antioxidant activity was analyzed by in vitro assays, and antimicrobial activity was investigated by the microdilution assay. The highest mycelial biomass yield was observed under blue-light cultivation. Many primordia arose under blue or green light, whereas the stroma was formed under red light. The presence of light altered the primary fungal metabolism, increasing the carbohydrate, tocopherol, fatty acid, and soluble sugar contents, mostly mannitol, and reducing the protein and organic acid concentrations. Cultivation under red light increased the phenol concentration. In contrast, cultivation under blue and green lights decreased phenol concentration. Benzoic and gallic acids were the main phenolic acids in the hydroalcoholic extracts, and the latter acids increased in all cultures under light, especially red light. Mycelial biomass cultivated under red light showed the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The ferric reducing antioxidant power (FRAP) method showed that all light wavelengths increased the antioxidant activity of mycelial biomass, with the highest value under red light. Moreover, the ß-carotene/linoleic acid co-oxidation (BCLA) assay demonstrated that the antioxidant activity was affected by light cultivation. Mycelial biomass grown under all conditions exhibited antibacterial and antifungal activities. Thus, mycelial biomass cultivation of L. crinitus under light conditions may be a promising strategy for controlling the mycelial chemical composition and biomass yield.

Emerging Antifungal Targets and Strategies.

Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

Synthetic and Natural Antifungals-Desirable and Hazardous Effects.

The increasing incidence of patients struggling with fungal infections, along with high losses in the production of different foods/crops due to fungal diseases presents a significant burden to healthcare, agronomy, and economies worldwide [...].

Hesperetin-Between the Ability to Diminish Mono- and Polymicrobial Biofilms and Toxicity.

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it's inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (<50% inhibition with MIC 4 mg/mL). Establishment of polymicrobial C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC50 0.340 mg/mL) and in brine shrimp lethality assay (LC50 > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.

Thiazolidin-4-Ones as Potential Antimicrobial Agents: Experimental and In Silico Evaluation.

Herein, we report computational and experimental evaluations of the antimicrobial activity of twenty one 2,3-diaryl-thiazolidin-4-ones. All synthesized compounds exhibited an antibacterial activity against six Gram-positive and Gram-negative bacteria to different extents. Thus, the MIC was in the range of 0.008-0.24 mg/mL, while the MBC was 0.0016-0.48 mg/mL. The most sensitive bacterium was S. Typhimurium, whereas S. aureus was the most resistant. The best antibacterial activity was observed for compound 5 (MIC at 0.008-0.06 mg/mL). The three most active compounds 5, 8, and 15, as well as compound 6, which were evaluated against three resistant strains, MRSA, P. aeruginosa, and E. coli, were more potent against all bacterial strains used than ampicillin. The antifungal activity of some compounds exceeded or were equipotent with those of the reference antifungal agents bifonazole and ketoconazole. The best activity was expressed by compound 5. All compounds exhibited moderate to good drug-likeness scores ranging from -0.39 to 0.39. The docking studies indicated a probable involvement of E. coli Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds. Finally, the assessment of cellular cytotoxicity of the compounds in normal human MRC-5 cells revealed that the compounds were not toxic.

Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.

BACKGROUND: Infectious diseases represent a significant global strain on public health security and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains. METHODS: Compounds were synthesized using the classical organic chemistry methods. Prediction of biological activity spectra was carried out using PASS and PASS-based web applications. Pharmacophore modeling in LigandScout software was used for quantitative modeling of the antibacterial activity. Antimicrobial activity was evaluated using the microdilution method. AutoDock 4.2® software was used to elucidate probable bacterial and fungal molecular targets of the studied compounds. RESULTS: All compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Three compounds were tested against resistant strains MRSA, P. aeruginosa and E. coli and were found to be more potent than MRSA than reference drugs. All compounds demonstrated a higher degree of antifungal activity than the reference drugs bifonazole (6-17-fold) and ketoconazole (13-52-fold). Three of the most active compounds could be considered for further development of the new, more potent antimicrobial agents. CONCLUSION: Compounds 5b (Z)-3-(3-hydroxyphenyl)-5-((1-methyl-1H-indol-3-yl)methylene)-2-thioxothiazolidin-4-one and 5g (Z)-3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-benzoic acid as well as 5h (Z)-3-(5-((5-methoxy-1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)benzoic acid can be considered as lead compounds for further development of more potent and safe antibacterial and antifungal agents.

Pyridylethanol(phenylethyl)amines are non-azole, highly selective Candida albicans sterol 14α-demethylase inhibitors.

Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The worldwide increase in the incidence of opportunistic fungal infections and the emerging resistance to available azole-based antifungal drugs, raise the need to develop structurally distinct and selective fungal CYP51 inhibitors. In this work we have, for the first time, investigated the binding of pyridylethanol(phenylethyl)amines to any fungal CYP51. The comparison of the binding to Candida albicans and human CYP51 studied by spectroscopic and modeling methods revealed moieties decisive for selectivity and potency and resulted in the development of highly selective derivatives with significantly increased inhibitory potency. The structure-based insight into the selectivity requirements of this new chemical class of fungal CYP51 inhibitors, their unique binding properties and the low molecular weight of lead derivatives offer novel directions for the targeted development of antifungal clinical candidates.

Synthesis and antimicrobial activity of new 2-piperazin-1-yl-N-1,3-thiazol-2-ylacetamides of cyclopenta[c]pyridines and pyrano[3,4-c]pyridines.

In this study, we report the synthesis and antimicrobial activity of some new disubstituted piperazines. Thus, 3-chlorocyclopenta[c]pyridines and 6-chloropyrano[3,4-c]pyridine 1 under mild reaction conditions with piperazine gave the 3(6)-piperazine-substituted cyclopenta[c]pyridines and pyrano[3,4-c]pyridine 2. Furthermore, the latter, by alkylation with 2-chloro-N-1,3-thiazol-2-ylacetamide, led to the formation of the target compounds. The evaluation of the antibacterial activity revealed that 3k was the most potent compound. The most sensitive bacterium was found to be Listeria monocytogenes, whereas Staphylococcus aureus was the most resistant one. Three compounds, 3d, 3g, and 3k, were tested also against the following resistant strains: methicillin-resistant S. aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. All three compounds appeared to be more potent than ampicillin against MRSA. Moreover, compound 3d showed a better activity than the reference drug ampicillin against P. aeruginosa, whereas 3g was more efficient against E. coli. The best antifungal activity was observed again for compound 3k. The most resistant fungi appeared to be Aspergillus fumigatus, whereas Trichoderma viride seemed the most sensitive one toward the compounds tested. Molecular docking studies on E. coli MurB, as well as on Candida albicans CYP51 and dihydrofolate reductase, were used for the prediction of the mechanisms of the antibacterial and antifungal activities, confirming the experimental results.

Camphor and Eucalyptol-Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity.

Candidaalbicans represents one of the most common fungal pathogens. Due to its increasing incidence and the poor efficacy of available antifungals, finding novel antifungal molecules is of great importance. Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have been explored previously. In this study, we examined their ability to inhibit the growth of different Candida species in suspension and biofilm, to block hyphal transition along with their impact on genes encoding for efflux pumps (CDR1 and CDR2), ergosterol biosynthesis (ERG11), and cytotoxicity to primary liver cells. Camphor showed excellent antifungal activity with a minimal inhibitory concentration of 0.125-0.35 mg/mL while eucalyptol was active in the range of 2-23 mg/mL. The results showed camphor's potential to reduce fungal virulence traits, that is, biofilm establishment and hyphae formation. On the other hand, camphor and eucalyptol treatments upregulated CDR1;CDR2 was positively regulated after eucalyptol application while camphor downregulated it. Neither had an impact on ERG11 expression. The beneficial antifungal activities of camphor were achieved with an amount that was non-toxic to porcine liver cells, making it a promising antifungal compound for future development. The antifungal concentration of eucalyptol caused cytotoxic effects and increased expression of efflux pump genes, which suggests that it is an unsuitable antifungal candidate.

Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation.

BACKGROUND: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. METHODS: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF3-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. RESULTS: All compounds showed antibacterial activity with MIC in range of 0.12-0.75 mg/mL and MBC at 0.25->1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. CONCLUSION: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF3 substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.

Antioxidant Extracts of Three Russula Genus Species Express Diverse Biological Activity.

This study explored the biological properties of three wild growing Russula species (R. integra, R. rosea, R. nigricans) from Serbia. Compositional features and antioxidant, antibacterial, antibiofilm, and cytotoxic activities were analyzed. The studied mushroom species were identified as being rich sources of carbohydrates and of low caloric value. Mannitol was the most abundant free sugar and quinic and malic acids the major organic acids detected. The four tocopherol isoforms were found, and polyunsaturated fatty acids were the predominant fat constituents. Regarding phenolic compounds, P-hydroxybenzoic and cinnamic acids were identified in the prepared methanolic and ethanolic extracts, which displayed antioxidant activity through the inhibition of thiobarbituric acid reactive substances (TBARS) formation and oxidative hemolysis; the highest activity was attributed to the R. nigricans ethanolic extract. This is the first report on the antibacterial and antibiofilm potential of the studied species, with the most promising activity observed towards Streptococcus spp. (0.20-0.78 mg/mL as the minimal inhibitory concentration, MIC). The most promising cytotoxic effect was caused by the R. integra methanolic extract on non-small cell lung cancer cells (NCI-H460). Therefore, due to the observed in vitro bioactive properties, the studied mushrooms arise as a source of functional ingredients with potential to be used in novel nutraceutical and drug formulations, which can be used in the treatment of various diseases and health conditions.

The Effect of Nitrogen Fertigation and Harvesting Time on Plant Growth and Chemical Composition of Centaurea raphanina subsp. mixta (DC.) Runemark.

The aim of the present study was to evaluate the effect of nitrogen fertigation (0, 200, 400, and 600 ppm of total nitrogen) and harvesting time (9 March 2018 and 19 April 2018) on the plant growth, chemical composition, and bioactive properties of Centaurea raphanina subsp. mixta plants. The highest yield of fresh leaves was observed for the treatment of 200 ppm of N without compromising nutritional value. The increasing nitrogen levels resulted in an increase of α- and total tocopherols and sugars content, especially in the second harvest for tocopherols and in the first harvest for sugars. Similarly, total organic acids and oxalic acid content increased with increasing nitrogen levels in both harvests, while fatty acids composition had a varied response to the tested factors. Pinocembrin neohesperidoside and pinocembrin acetyl neohesperidoside isomer II were the most abundant phenolic compounds with the highest content being observed in the control treatment of the first and second harvest, respectively. The highest antioxidant activity was observed for the control and the 600 ppm treatments of the second harvest for the OxHLIA and TBARS assays, respectively, probably due to the high content of pinocembrin acetyl neohesperidoside isomer II and α-tocopherol, respectively. Finally, cytotoxic effects and antimicrobial properties showed a varied response depending on the treatment. In conclusion, C. raphanina subsp. mixta has low requirements of nitrogen to achieve the highest yield, while a varied response to the tested fertigation treatments and harvesting time was observed in terms of the chemical composition and the bioactive properties.

Chemical Composition and Plant Growth of Centaurea raphanina subsp. mixta Plants Cultivated under Saline Conditions.

The aim of this report was to study the effect of salinity (control: 2dS/m, S1: 4 dS/m and S2: 6 dS/m) and harvest time (first harvest on 9 May 2018 and second harvest on 19 April 2018) on the growth and the chemical composition of Centaurea raphanina subsp. mixta plants. The plants of the first harvest were used for the plant growth measurements (fresh weight and moisture content of leaves, rosette diameter, number and thickness of leaves), whereas those of the second harvest were not used for these measurements due to the flowering initiation, which made the leaves unmarketable due to their hard texture. The results of our study showed that C. raphanina subsp. mixta plants can be cultivated under mild salinity (S1 treatment) conditions without severe effects on plant growth and yield, since a more severe loss (27.5%) was observed for the S2 treatment. In addition, harvest time proved to be a cost-effective cultivation practice that allows to regulate the quality of the final product, either in edible form (first harvest) or for nutraceutical and pharmaceutical purposes as well as antimicrobial agents in food products. Therefore, the combination of these two agronomic factors showed interesting results in terms of the quality of the final product. In particular, high salinity (S2 treatment) improved the nutritional value by increasing the fat, proteins and carbohydrates contents in the first harvest, as well as the tocopherols and sugars contents (S1 and S2 treatments, respectively) in the second harvest. In addition, salinity and harvest time affected the oxalic acid content which was the lowest for the S2 treatment at the second harvest. Similarly, the richest fatty acid (α-linolenic acid) increased with increasing salinity at the first harvest. Salinity and harvest time also affected the antimicrobial properties, especially against Staphylococcus aureus, Bacillus cereus and Trichoderma viride, where the extracts from the S1 and S2 treatments showed high effectiveness. In contrast, the highest amounts of flavanones (pinocembrin derivatives) were detected in the control treatment (second harvest), which was also reflected to the highest antioxidant activity (TBARS) for the same treatment. In conclusion, C. raphanina subsp. mixta plants seem to be tolerant to medium salinity stress (S1 treatment) since plant growth was not severely impaired, while salinity and harvesting time affected the nutritional value (fat, proteins, and carbohydrates) and the chemical composition (tocopherols, sugars, oxalic acid, fatty acids), as well as the bioactive properties (cytotoxicity and antimicrobial properties) of the final product.

Novel Hit Compounds as Putative Antifungals: The Case of Aspergillus fumigatus.

The prevalence of invasive fungal infections has been dramatically increased as the size of the immunocompromised population worldwide has grown. Aspergillus fumigatus is characterized as one of the most widespread and ubiquitous fungal pathogens. Among antifungal drugs, azoles have been the most widely used category for the treatment of fungal infections. However, increasingly, azole-resistant strains constitute a major problem to be faced. Towards this direction, our study focused on the identification of compounds bearing novel structural motifs which may evolve as a new class of antifungals. To fulfil this scope, a combination of in silico techniques and in vitro assays were implemented. Specifically, a ligand-based pharmacophore model was created and served as a 3D search query to screen the ZINC chemical database. Additionally, molecular docking and molecular dynamics simulations were used to improve the reliability and accuracy of virtual screening results. In total, eight compounds, bearing completely different chemical scaffolds from the commercially available azoles, were proposed and their antifungal activity was evaluated using in vitro assays. Results indicated that all tested compounds exhibit antifungal activity, especially compounds 1, 2, and 4, which presented the most promising minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values and, therefore, could be subjected to further hit to lead optimization.

The Effects of Biostimulants, Biofertilizers and Water-Stress on Nutritional Value and Chemical Composition of Two Spinach Genotypes (Spinacia oleracea L.).

In the present study, the effect of biostimulants application on the nutritional quality and bioactive properties of spinach cultivated in protected environment under water stress conditions was evaluated. For this purpose, four commercially available biostimulant products (Megafol (MEG), Aminovert (AM), Veramin Ca (V), Twin Antistress (TA), and two spinach genotypes (Fuji F1 and Viroflay) were tested under two irrigation regimes (normal irrigation (W+), and water-holding (W-). Fat and carbohydrates content was favored by water stress when Megafol (MEGW+) and Veramin (VW+) were applied on Fuji plants, while calorific value was also increased by MEGW+ treatment. In contrast, protein and ash content increased when AMW- and TAW+ were applied on Viroflay plants. Raffinose and glucose were the most abundant sugars, followed by sucrose and fructose, with the highest contents recorded for Fuji plants when AMW+ (fructose, glucose and total carbohydrates), CW- (sucrose), and TAW- (raffinose) treatments were applied. Regarding organic acids, oxalic and malic acid which had the highest contents for the TAW- (Viroflay plants) and AMW- (Fuji plants) treatments, respectively. α- and γ-tocopherol were the only isoforms detected with MEGW- and VW- inducing the biosynthesis of α-tocopherol, while AMW+ increased γ-tocopherol content in Fuji plants. The main fatty acids were α-linolenic and linoleic acids which were detected in the highest amounts in AMW-, AMW+, and TAW+ the former and in AMW-, VW-, and CW+ the latter. Regarding phenolic compounds content, peak 12 (5,3',4'-Trihydroxy-3-methoxy-6:7-methylenedioxyflavone-4'-glucuronide) was the most abundant compound, especially in Viroflay plants under normal irrigation and no biostimulants added (CW-). The antioxidant and cytotoxic activity of the tested samples did not show promising results when compared with the positive controls, while a variable antibacterial activity was recorded depending on the tested biostimulant, irrigation regime and genotype. In conclusion, a variable effect of the tested biostimulants and irrigation regimes was observed on bioactive properties and chemical composition of both spinach genotypes which highlights the need for further research in order to make profound conclusions regarding the positive effects of biostimulants under water stress conditions.

Plant Flavonoids as Reservoirs of Therapeutics against Microbial Virulence Traits: A Comprehensive Review Update.

Flavonoids are secondary metabolites abundantly present in plants and, in most cases, essential contributors to plants bioactivity. They have been studied so far for a range of possible health-beneficial effects, including antioxidant, cardioprotective, and cytotoxic. Therefore, there are data on the antimicrobial potential of a significant number of flavonoids. However, less is known regarding their antivirulence traits. Trending antimicrobial research worldwide has pointed out the promising effects of antimicrobial strategies based on the antivirulence principle, so this review aims to present the newest research regarding the antivirulence effects of flavonoids. Articles on antivirulence flavonoids published from 2015 until now were selected. A range of molecules from this class has been studied up to date, with the most abundant data for quercetin and myricetin, while the most studied organism is Pseudomonas aeruginosa. The antivirulence attributes studied included antibiofilm assessment, followed by data on the inhibition of virulence pigments (pyocyanin, violacein, and staphyloxanthin) and virulence enzyme production (such as sortase A and elastase). Less information is collected on the inhibition of morphological transition, motility, and molecular mechanisms underlying the antivirulence properties of flavonoids and in vivo research. Flavonoids are a group of compounds with a wide range of antivirulence traits and might be further developed into essential parts of novel antimicrobial strategies.

A Comparative Study of Lactarius Mushrooms: Chemical Characterization, Antibacterial, Antibiofilm, Antioxidant and Cytotoxic Activity.

Mushrooms are valued worldwide for their nutritional, organoleptic and chemical properties. The aim of this study was to determine the chemical composition (free sugars, organic acids, fatty acids, tocopherols and phenolic compounds) and bioactivity of three wild mushrooms (Lactarius piperatus, Lactarius quietus and Lactarius vellereus) from Serbia. Chemical analysis was performed with HPLC-RI and UFLC-PDA (for hydrophilic compounds) and with GC-FID and HPLC-FP (for lipophilic compounds). The analysis of phenolic compounds was performed by UFLC-DAD. Biological activities were evaluated using three different assays (microdilution, TBARS and SRB assays). The results showed that the fruiting bodies were rich in mannitol and trehalose. The main organic acids were oxalic acid and citric acid. As for lipophilic components, stearic, oleic and linoleic acids and ß-tocopherol dominated in all the species studied. In addition, the methanolic and ethanolic extracts obtained showed antibacterial, antibiofilm and antioxidant properties. As for cytotoxicity, the extracts were not toxic or only moderately toxic toward different tumor cell lines. According to the results, the selected Serbian mushrooms are a rich source of bioactive compounds, and due to their good biological potential, they can be further exploited as functional ingredients beneficial to human health (antimicrobial agents, antioxidants).

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents-In Silico and In Vitro Evaluation.

Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate derivatives. All tested compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin as well as streptomycin by 10-50 fold. The most sensitive bacterium was En. Cloacae, while E. coli was the most resistant one, followed by M. flavus. The most active compound appeared to be compound 8 with MIC at 0.004-0.03 mg/mL and MBC at 0.008-0.06 mg/mL. The antifungal activity of tested compounds was good to excellent with MIC in the range of 0.004-0.06 mg/mL, with compound 15 being the most potent. T. viride was the most sensitive fungal, while A. fumigatus was the most resistant one. Docking studies revealed that the inhibition of E. coli MurB is probably responsible for their antibacterial activity, while 14a-lanosterol demethylase of CYP51Ca is involved in the mechanism of antifungal activity. Furthermore, drug-likeness and ADMET profile prediction were performed. Finally, the cytotoxicity studies were performed for the most active compounds using MTT assay against normal MRC5 cells.

Solvent System-Guided Extraction of Centaurium spicatum (L.) Fritch Provides Optimized Conditions for the Biological and Chemical Characteristics of the Herbal Extracts.

Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.

Purple tea: chemical characterization and evaluation as inhibitor of pancreatic lipase and fat digestion in mice.

A variety of the classic green tea plant, Camellia sinensis, was developed and is exclusive to Kenya. Due to high content of anthocyanin polyphenols in its leaves, the beverage obtained from this variety is purple in color and is the origin of the name purple tea. This work had two main purposes. The first one was to identify and quantify the major anthocyanin polyphenols in a hot water aqueous extract of the purple tea leaves. The second one was to test the hypothesis if this extract is capable of inhibiting triglyceride absorption considering that anthocyanin polyphenolics have been frequently associated to antilipidemic effects. Parallel experiments were always done with a similar green tea extract for comparison purposes. The antioxidant, anti-inflammatory, and cytotoxic activities of both tea varieties are similar. The purple tea extract, however, was strongly inhibitory toward the pancreatic lipase (minimal IC50 = 67.4 µg mL-1), whereas the green tea preparation was a weak inhibitor. Triglyceride digestion in mice was inhibited by the purple tea extract starting at 100 mg kg-1 dose and with a well-defined dose dependence. Green tea had no effect on triglyceride digestion at doses up to 500 mg kg-1. The latter effect is probably caused by several components in the purple tea extract including non-anthocyanin and anthocyanin polyphenols, the first ones acting solely via the inhibition of the pancreatic lipase and the latter by inhibiting both the lipase and the transport of free fatty acids from the intestinal lumen into the circulating blood. The results suggest that the regular consumption of Kenyan purple tea can be useful in the control of obesity.