New 1H-1,2,4-Triazolyl Derivatives as Antimicrobial Agents.

New 1H-1,2,4-triazolyl derivatives were synthesized, and six of them were selected based on docking prediction for the investigation of their antimicrobial activity against five bacterial and eight fungal strains. All compounds demonstrated antibacterial activity with MIC lower than that of the ampicillin and chloramphenicol. In general, the most sensitive bacteria appeared to be P. fluorescens, while the plant pathogen X. campestris was the most resistant. The antifungal activity of the compounds was much better than the antibacterial activity. All compounds were more potent (6 to 45 times) than reference drugs ketoconazole and bifonazole with the best activity achieved by compound 4 a. A. versicolor, A. ochraceus, A.niger, and T.viride showed the highest sensitivity to compound 4 b, while, T. viride, P. funiculosum, and P.ochrochloron showed good sensitivity to compound 4 a. Molecular docking studies suggest that the probable mechanism of antibacterial activity involves the inhibition of the MurB enzyme of E. coli, while CYP51 of C. albicans appears to be involved in the mechanism of antifungal activity. It is worth mentioning that none of the tested compounds violated Lipinski's rule of five.

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.

Antimicrobial Activity of Some Steroidal Hydrazones.

Twelve steroid based hydrazones were in silico evaluated using computer program PASS as antimicrobial agents. The experimental evaluation revealed that all compounds have low to moderate antibacterial activity against all bacteria tested, except for B. cereus with MIC at a range of 0.37-3.00 mg/mL and MBC at 0.75-6.00 mg/mL. The most potent appeared to be compound 11 with MIC/MBC of 0.75/1.5 mg/mL, respectively. The evaluation of antibacterial activity against three resistant strains MRSA, E. coli and P. aeruginosa demonstrated superior activity of compounds against MRSA compared with ampicillin, which did not show bacteriostatic or bactericidal activities. All compounds exhibited good antifungal activity with MIC of 0.37-1.50 mg/mL and MFC of 1.50-3.00 mg/mL, but with different sensitivity against fungi tested. According to docking studies, 14-alpha demethylase inhibition may be responsible for antifungal activity. Two compounds were evaluated for their antibiofilm activity. Finally, drug-likeness and docking prediction were performed.

Pygidial glands of the blue ground beetle Carabus intricatus: chemical composition of the secretion and its antimicrobial activity.

Pygidial gland secretions are used as repellent defensive allomones in ground beetles. We provide the first precise data on the chemical composition and antimicrobial potency of the secretion of the blue ground beetle, as well as on the morphology of its pygidial glands. The latter structures were not previously studied chemoecologically and morphologically, and we hypothesized that their secretion may have some antimicrobial action, as is the case with certain Carabus species. Gas chromatography-mass spectrometry (GC-MS) was used to identify methacrylic and angelic acids as dominant chemicals in the secretion from individuals of three populations of the blue ground beetle in Serbia. We tested its secretion against selected strains of medically important microorganisms. The secretion exibits antimicrobial action against certain bacterial species and all tested micromycetes. The most significant antifungal effect of the secretion was against Penicillium ochrochloron, which is more sensitive to the secretion than to commercial antifungal drugs ketoconazole and bifonazole. Bifonazole achieved minimum inhibitory concentrations against Trichoderma viride at more than three times higher value than did the secretion, indicating a significant antifungal effect of the secretion against this micromycete as well. Additionally, we tested commercially available standards of two dominant chemicals in the secretion to investigate their interaction and antimicrobial role in the secretion. Finally, we describe all glandular morpho-functional units of the blue ground beetle. Our results suggest that the secretion of the blue ground beetle may serve not only defensive but also antimicrobial functions, which likely aid the survival of this beetle in the microbial-rich forest litter habitat.

Antimicrobial and Cytotoxic Activities of Selected Hieracium L. s. str. (Asteraceae) Extracts and Isolated Sesquiterpene Lactones.

Antimicrobial and cytotoxic activities were tested for dried MeOH extracts of Hieracium calophyllum (CAL), H. coloriscapum (COL), H. pseudoschenkii (PSE), H. valdepilosum (VAL) and H. glabratum (GLA) herbs (flowering aerial parts), their 2 sesquiterpene lactones (SLs) 8-epiixerisamine A and crepiside E, and dried CH2 Cl2 extract of H. scheppigianum (SCH) herb. In microdilution test, extracts showed activity on all tested microorganisms (8 bacteria, 10 fungi). The best effect was exhibited by SCH and CAL on Salmonella Typhimurium (MIC=1.7-2.5 mg/mL MBC=3.4-5.0 mg/mL), and SCH and VAL on Candida albicans (MIC=2.5 mg/mL MFC=5.0 mg/mL). SLs showed notable effect on all tested fungi Aspergillus ochraceus, Penicillium funiculosum, C. albicans and C. krusei (MIC=0.15-0.4 mg/mL MFC=0.3-0.8 mg/mL). In MTT test, extracts inhibited growth of all tested cancer cells (HeLa, LS174 and A549), with the best effect on HeLa (IC50 =148.1 µg/mL for SCH, and 152.3-303.2 µg/mL for MeOH extracts); both SLs were active against HeLa cells (IC50 =46.2 µg/mL for crepiside E and 103.8 µg/mL for 8-epiixerisamine A). Extracts and SLs showed good safety profile on normal MRC-5 cells.

Hieracium waldsteinii (Asteraceae) and Onosma stellulata (Boraginaceae) as a Source of Antioxidant and Antimicrobial Agents.

The current study aimed to phytochemically characterize (including a detailed phenolic profile) two endemic Balkan's species (Hieracium waldsteinii and Onosma stellulata) and determine their possible application as a source of natural antioxidant and antimicrobial agents. The main phenolic compound in both species (in all examined parts) was chlorogenic acid. Eriodictyol, genistein and naringenin were quantified only in H. waldsteinii while isorhamnetin-3-O-rutinoside and sinapic acid were characteristic for O. stellulata. The highest antioxidant activity (98 mg AAE/g dry weight for TAC assay) was ascribed to the flower extract of H. waldsteinii while the lowest results (∼4.3 mg AAE/g dry weight for FRP assay) were exhibited by the extracts obtained from the plant's stem. Antimicrobial assays showed moderate antibacterial, i. e., moderate/strong activity against several tested fungi (in particular Trichoderma viride). Correlation analysis revealed strong positive connection between phenolic compounds and reducing power of extracts as well as between total phenolic and flavonoid content and the obtained minimal inhibitory concentration recorded in antibacterial assays.

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.

Towards the Optimization of Microwave-Assisted Extraction and the Assessment of Chemical Profile, Antioxidant and Antimicrobial Activity of Wine Lees Extracts.

Wine lees, a sub-exploited byproduct of vinification, is considered a rich source of bioactive compounds, such as (poly)phenols, anthocyanins and tannins. Thus, the effective and rapid recovery of these biomolecules and the assessment of the bioactive properties of wine lees extracts is of utmost importance. Towards this direction, microwave-assisted extraction (MAE) factors (i.e., extraction time, microwave power and solvent/material ratio) were optimized using experimental design models in order to maximize the (poly)phenolic yield of the extracts. After optimizing the MAE process, the total phenolic content (TPC) as well as the antiradical, antioxidant and antimicrobial activity of the extracts were evaluated. Furthermore, Fourier transform infrared spectroscopy (FTIR) was employed to investigate the chemical profile of wine lees extracts. Red varieties exhibited higher biological activity than white varieties. The geographical origin and fermentation stage were also considered as critical factors. The white variety Moschofilero presented the highest antioxidant, antiradical and antimicrobial activity, while Merlot and Agiorgitiko samples showed noteworthy activities among red varieties. Moreover, IR spectra confirmed the presence of sugars, amino acids, organic acids and aromatic compounds. Thus, an efficient, rapid and eco-friendly process was proposed for further valorization of wine lees extracts.

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.

From Tradition to Health: Chemical and Bioactive Characterization of Five Traditional Plants.

Several scientific studies have been proving the bioactive effects of many aromatic and medicinal plants associated with the presence of a high number of bioactive compounds, namely phenolic compounds. The antioxidant, anti-inflammatory, and antimicrobial capacities of these molecules have aroused high interest in some industrial sectors, including food, pharmaceuticals, and cosmetics. This work aimed to determine the phenolic profiles of the infusions and hydroethanolic extracts of five plants (Carpobrotus edulis, Genista tridentata, Verbascum sinuatum, Cytisus multiflorus, and Calluna vulgaris) that have been employed in many traditional preparations. In addition, the antioxidant, antimicrobial, anti-inflammatory, and anti-tumoral activity of each different preparation was evaluated using in vitro assays. The HPLC-DAD-ESI/MS profile revealed the presence of eighty phenolic compounds, belonging to seven different families of compounds. Regarding antioxidant properties, the hydroethanolic extract of C. edulis showed a potent effect in the TBARS assay (IC50 = 1.20 µg/mL), while G. tridentata hydroethanolic extract achieved better results in the OxHLIA test (IC50 = 76 µg/mL). For cytotoxic and anti-inflammatory results, V. sinuatum infusions stood out significantly, with GI50 = 59.1-92.1 µg/mL and IC50 = 121.1 µg/mL, respectively. Finally, C. edulis hydroethanolic extract displayed the most relevant antibacterial activity, showing MBC values of 0.25-1 mg/mL, while G. tridentata hydroethanolic extract exerted the greatest antifungal effects (MFC of 0.5-1 mg/mL). The results of this study deepen the knowledge of the phenolic profiles and also provide evidence on the bioactive properties of the species selected, which could be considered highly valuable options for research and application in several sectors, namely food, cosmetics, and pharmaceuticals.

Basidiocarp structures of Lentinus crinitus: an antimicrobial source against foodborne pathogens and food spoilage microorganisms.

Lentinus crinitus basidiocarps are an alternative to antimicrobials, but the stipe (24% basidiocarp) is discarded even with potential antimicrobial activity. This study evaluated the antimicrobial activity of L. crinitus basidiocarp pileus and stipe extracts against foodborne pathogens and food spoilage microorganisms. Basidiocarps of L. crinitus were grown in sugarcane bagasse and rice husks and the pileus and stipe methanolic extract was analyzed by broth microdilution method for antimicrobial activity against eight bacteria and eight fungi. The minimum bactericidal concentration values for pileus and stipe ranged from 0.40 to 0.50 mg mL- 1, for streptomycin from 0.10 to 0.50 mg mL- 1, and for ampicillin from 0.40 to 1.20 mg mL- 1. The minimum fungicidal concentration values for pileus and stipe ranged from 0.06 to 0.60 mg mL- 1, for bifonazole from 0.20 to 0.25 mg mL- 1, and for ketoconazole from 0.30 to 3.50 mg mL- 1. Extracts had bacteriostatic, bactericidal, fungistatic and fungicidal activity against all microorganisms, but with greater efficiency and specificity for some microorganisms. Both pileus and stipe are promising and sustainable alternatives for use in food, agricultural, and pharmaceutical industries.

2-Aryl-3-(6-trifluoromethoxy)benzo[d]thiazole-based thiazolidinone hybrids as potential anti-infective agents: Synthesis, biological evaluation and molecular docking studies.

The search for new antimicrobial agents is greater than ever due to the perpetual threat of multidrug resistance in known pathogens and the relentless emergence of new infections. In this manuscript, ten thiazole-based thiazolidinone hybrids bearing a 6-trifluoromethoxy substituent on the benzothiazole core were synthesized and evaluated against a panel of four bacterial strains Salmonella typhimurium, Staphylococcus aureus, Escherichia coli and Listeria monocytogenes and three resistant strains Pseudomonas aeruginosa, E. coli and MRSA. The evaluation of minimum bactericidal and minimum inhibitory concentrations was accomplished by microdilution assay. As reference compounds ampicillin and streptomycin were employed. All compounds displayed antibacterial efficiencies with MBCs/MICs at 0.25-1 mg/mL and 0.12-1 mg/mL respectively while ampicillin displayed MBCs/MICs at 0.15-0.3 mg/mL and at 0.1-0.2 mg/mL respectively. MICs/MBC of streptomycin varied from 0.05 to 0.15 mg/mL and from 0.1 to 0.3 mg/mL respectively. The best overall effect was observed for compound h4, while compound h1 exhibited the highest effective action against E. coli (MIC/MBC 0.12/0.25 mg/ml) among all tested compounds.

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, biological evaluation and QSAR studies of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives as antimicrobial and antifungal agents.

A series of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives were synthesized and evaluated for their activity against four gram-positive and four gram-negative bacterial and eight fungal species. The majority of the compounds exhibited excellent antimicrobial and antifungal activity, being more potent than the control compounds. Compound 22, bearing a m-methoxyphenyl group and an ethylenediamine side chain anchored at C-2 of the thienopyrimidinone core, is the most potent antibacterial compound with broad antimicrobial activity with MIC values in the range of 0.05-0.13 mM, being 6 to 15 fold more potent than the controls, streptomycin and ampicillin. Furthermore, compounds 14 and 15 which bear a p-chlorophenyl and m-methoxyphenyl group, respectively, and share a 2-(2-mercaptoethoxy)ethan-1-ol side chain showed the best antifungal activity, being 10-15 times more potent than ketoconazole or bifonazole with MIC values 0.013-0.026 and 0.027 mM, respectively. Especially in the case of compound 15 the low MIC values were accompanied by excellent MFC values ranging from 0.056 to 0.058 mM. Evaluation of toxicity in vitro on HFL-1 human embryonic primary cells and in vivo in the nematode C. elegans revealed no toxic effects for both compounds 15 and 22 tested at the MIC concentrations. Ligand-based similarity search and molecular docking predicted that the antibacterial activity of analogue 22 is related to inhibition of the topoisomerase II DNA gyrase enzyme and the antifungal activity of compound 15 to CYP51 lanosterol demethylase enzyme. R-Group analysis as a means of computational structure activity relationship tool, highlighted the compounds' crucial pharmacophore features and their impact on the antibacterial and antifungal activity. The presence of a N-methyl piperidine ring fused to the thienopyrimidinone core plays an important role in both activities.

A Prospective of Multiple Biopharmaceutical Activities of Procyanidins-Rich Uapaca togoensis Pax Extracts: HPLC-ESI-TOF-MS Coupled with Bioinformatics Analysis.

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.

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.

Chemical Composition and Bioactive Characterisation of Impatiens walleriana.

The attractive colour characteristics of the flowers of the species Impatiens walleriana have been arousing great interest in the food industry, which is looking for potential natural sources of colouring ingredients. In this sense, the present work focused on the chemical and bioactive characterization of pink and orange flowers of I. walleriana. The phenolic compounds were determined by HPLC-DAD-ESI/MS; in addition, different bioactivities (antioxidant, antimicrobial, anti-inflammatory and cytotoxicity) were also analysed. Both samples studied showed significant amounts of phenolic compounds, especially phenolic acids, flavonoids, and anthocyanins, which justifies the excellent performance in the different bioactivities studied. The orange variety, despite having a greater variety of phenolic compounds, showed a total amount of compounds lower than the pink variety. Overall, the flowers of I. walleriana emerge as a promising resource to be explored by the food industry.

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.