Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols (3a-3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and the evaluation of their antifungal activity. In silico prediction of biological activity with computer program PASS indicate that the compounds have a high novelty compared to the known antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k, followed by 3n. Their MIC values for different fungi were 22.1-184.2 and 71.3-199.8 µM, respectively. Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular docking studies on C. albicans sterol 14α-demethylase (CYP51) and DNA topoisomerase IV were used to predict the mechanism of antifungal activities. According to the docking results, the inhibition of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We also showed that most active compounds have a low cytotoxicity, which allows us to consider them promising antifungal agents for the subsequent testing activity in in vivo assays.

• Klíčová slova
• C. albicans CYP51, PASS, antifungal activity, chromenol, molecular docking, vinyl-1,2,4-triazole,
• MeSH
• antifungální látky * chemická syntéza   chemie   farmakologie   MeSH
• chromony * chemická syntéza   chemie   farmakologie   MeSH
• Hypocreales růst a vývoj   MeSH
• mitosporické houby růst a vývoj   MeSH
• preklinické hodnocení léčiv MeSH
• simulace molekulového dockingu * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky * MeSH
• chromony * MeSH

Both natural and synthetic substances are conveniently used for studying metabolism, genetic aspects, morphogenesis of cell structures, life cycle and differentiation of fungi.

• MeSH
• antifungální látky farmakologie   MeSH
• buněčná diferenciace MeSH
• houby účinky léků   genetika   metabolismus   MeSH
• morfogeneze MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antifungální látky MeSH

A number of papers reporting antimicrobial properties of extracts, essential oils, resins and various classes of compounds isolated from higher plants have been published in recent years; however, a comprehensive analysis of plant-derived antimicrobial agents currently applied in practice for the improvement of human health is still lacking. This review summarizes data on clinical efficacy, antimicrobial effects and the chemistry of commercially available antibacterial and antifungal agents of plant origin currently used in the prevention and treatment of gastrointestinal, oral, respiratory, skin, and urinary infections. As a result of an analysis of the literature, more than 40 plant-derived over-the-counter pharmaceuticals, dietary supplements, cosmetics, herbal medicines, and functional foods containing complex mixtures (e.g. Glycyrrhiza glabra extract, Melaleuca alternifolia essential oil, and Pistacia lentiscus resin), pure compounds (e.g. benzoic acid, berberine, eucalyptol, salicylic acid and thymol) as well as their derivatives and complexes (e.g. bismuth subsalicylate and zinc pyrithione) have been identified. The effectiveness of many of these products is illustrated by results of clinical trials and supported by data on there in vitro antimicrobial activity. A broad spectrum of various commercial products currently available on the market and their welldocumented clinical efficacy suggests that plants are prospective sources for the identification of new types of antimicrobial agents in future. Innovative approaches and methodologies for effective proof-of-concept research and the development of new types of plant-derived products effective against recently emerging problems related to human microbial diseases (e.g. antimicrobial resistance) are also proposed in this review.

• Klíčová slova
• Plant, antibacterial, antifungal, commercial products, compound, essential oil, extract.,
• MeSH
• antibakteriální látky chemie   farmakologie   terapeutické užití   MeSH
• antifungální látky chemie   farmakologie   terapeutické užití   MeSH
• biologické přípravky chemie   farmakologie   terapeutické užití   MeSH
• Glycyrrhiza chemie   MeSH
• lidé MeSH
• Melaleuca chemie   MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• Pistacia chemie   MeSH
• rostlinné extrakty chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• biologické přípravky MeSH
• rostlinné extrakty MeSH

The growth-inhibitory effect of 9 antifungal agents against 32 strains of aspergilli belonging to 10 species was studied. MIC values were determined in a microtiter dilution method using Brain Heart Infusion Broth (polyenes, azoles) and a medium with Yeast Nitrogen Base (5-flucytosine). Saperconazole was the most active agent against all isolates tested, the growth of 90% being inhibited at a concentration of 0.09 mg l-1. The susceptibility profile of individual species differed only little, with the exception of high MIC values of polyenes in A. terreus. Nine isolates (28%) were resistant to 5-flucytosine. The intra-species variation of susceptibility studied in A. fumigatus was only little pronounced.

• MeSH
• antibiotická rezistence MeSH
• antifungální látky farmakologie   MeSH
• Aspergillus účinky léků   růst a vývoj   izolace a purifikace   MeSH
• druhová specificita MeSH
• inhibitory růstu farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antifungální látky MeSH
• inhibitory růstu MeSH

The alkaloids N-methylhydrasteine hydroxylactam and 1-methoxyberberine chloride were isolated from Corydalis longipes. Both alkaloids showed high efficacy individually (in concentration of 50-150 ppm) and also in a 1:1 mixture against spore germination of some fungi, viz. Alternaria alternata, A. brassicae, Curvularia maculans, Curvularia sp., Colletotrichum gloeosporioides, Colletotrichum sp., Helminthosporium speciferum, H. pennisetti, Helminthosporium sp., and Ustilago cynodontis. The antifungal effect of single compounds was dose-dependent. If the mutual ratio of the two components in the mixture was changed from 1:1 to a major content of any of the two compounds, the inhibitory effect on spore germination decreased.

• MeSH
• alkaloidy chemie   izolace a purifikace   farmakologie   MeSH
• antifungální látky chemie   izolace a purifikace   farmakologie   MeSH
• Corydalis chemie   MeSH
• houby účinky léků   růst a vývoj   MeSH
• rostlinné přípravky chemie   MeSH
• spory hub účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy MeSH
• antifungální látky MeSH
• rostlinné přípravky MeSH

• MeSH
• antifungální látky * MeSH
• Arthrodermataceae účinky léků   MeSH
• houby účinky léků   MeSH
• kvasinky účinky léků   MeSH
• nitrofurany farmakologie   MeSH
• thiazoly farmakologie   MeSH
• thiofeny farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky * MeSH
• nitrofurany MeSH
• thiazoly MeSH
• thiofeny MeSH

UNLABELLED: In recent years, increased rates of yeast infections in humans and animals have been recognized worldwide. Since animals may represent a source of yeast infections for humans, knowing the antifungal susceptibility profile of yeast isolates from milk and evaluating their pathogenic potential would be of great medical importance. Therefore, the aim of this survey was to study yeast diversity in milk samples, analyze the hemolytic and phospholipase activities of isolates and determine minimal inhibition concentration (MIC) for fluconazole, voriconazole and flucytosine. Out of 66 yeast isolates obtained from 910 individual raw milk samples from subclinically infected cows, 26 different yeast species were determined based on sequencing of the D1/D2 and ITS regions. Among them, Pichia kudriavzevii (formerly known as Candida krusei), Kluyveromyces marxianus (formerly known as Candida kefyr) and Debaryomyces hansenii (formerly known as Candida famata) were the most commonly identified. Hemolysin and/or phospholipase activity was observed in 66.7% of isolates. The elevated MIC for fluconazole was determined in 16 isolates from 11 species. The findings of this study demonstrate that yeast isolates from raw milk have the potential to express virulence attributes such as hemolysin and phospholipase, and additionally, some of these strains showed elevated MIC to fluconazole or to flucytosine. LAY SUMMARY: We identified 66 yeast isolates, including 26 different yeast species from 910 individual milk samples. Our results indicate that individual milk samples may serve as a source of yeasts with the potential to trigger infection and may have reduced sensitivity to tested antifungal agents.

• Klíčová slova
• Candida sp, antifungal susceptibility, mastitis, milk, virulence factors, yeast,
• MeSH
• antifungální látky * farmakologie   MeSH
• faktory virulence * genetika   MeSH
• flukonazol farmakologie   MeSH
• mikrobiální testy citlivosti veterinární   MeSH
• mléko MeSH
• skot MeSH
• vorikonazol MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky * MeSH
• faktory virulence * MeSH
• flukonazol MeSH
• vorikonazol MeSH

A series of 4-alkylthiopyridine-2-carbothioamides have been prepared and evaluated in vitro for antimicrobial activity. Chemical structures have been demonstrated by IR and 1H NMR data and by elemental analysis. The antimycobacterial activity of these compounds against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium, and Mycobacterium fortuitum, and the antifungal activity against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Trichophyton mentagrophytes, Aspergillus fumigatus, and Absidia corymbifera were determined by the MIC values. Compounds 3 exhibit good antimycobacterial activity compared to isoniazide. A moderate antifungal activity was observed against T. mentagrophytes. Activity is influenced by hydrophobicity of the alkyl group.

• MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• antiinfekční látky chemická syntéza   farmakologie   MeSH
• magnetická rezonanční spektroskopie MeSH
• mikrobiální testy citlivosti MeSH
• pyridiny chemická syntéza   chemie   farmakologie   MeSH
• thioamidy chemická syntéza   chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antifungální látky MeSH
• antiinfekční látky MeSH
• pyridiny MeSH
• thioamidy MeSH

The present review paper deals with novel antifungal drugs. The lack of new antifungal drugs ascend proportionally to the increasing occurrence of serious infections caused by yeast and fungi mainly at immunocompromised or in other way sensitive patients. The topical state of pharmacotherapy is briefly drawn out; most attention is given to newly developed active entities. Established agents do not satisfy the medical need completely, azoles are fungistatic and vulnerable to resistance, whereas polyenes cause serious host toxicity. Drugs in clinical development include modified azoles and a new class of echinocandins and pneumocandins. Other promising novel agents in preclinical development include several inhibitors of fungal protein, lipid and cell wall syntheses.

• MeSH
• antifungální látky * chemie   farmakologie   MeSH
• chemie farmaceutická MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antifungální látky * MeSH

The ability of C. parapsilosis (an important cause of nosocomial infections) to produce biofilm was evaluated in 32 bloodstream isolates and 85 strains isolated from skin. The biofilm formation was found in 19 (59%) blood isolates and only in 33 (39%) isolates from skin. The antifungal susceptibility was assessed for amphotericin B, itraconazole and voriconazole in planktonic and biofilm form of the 19 biofilm-positive bloodstream strains by broth microdilution method according to NCCLS standards. The method was modified by the use of resazurin as a colorimetric indicator of the metabolically active cells which makes the determination of the effect of antifungal agents easier. Biofilm forms of all strains were more resistant than their planktonic form.

• MeSH
• antifungální látky farmakologie   MeSH
• biofilmy účinky léků   MeSH
• Candida účinky léků   patogenita   MeSH
• fungální léková rezistence účinky léků   MeSH
• fungemie farmakoterapie   MeSH
• infekce spojené se zdravotní péčí mikrobiologie   MeSH
• kolorimetrie MeSH
• lidé MeSH
• mikrobiální testy citlivosti metody   MeSH
• mikrobiologické techniky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antifungální látky MeSH