High Fungistatic Activity Research Articles

Synthesis and Antimicrobial Activity of New Mannich Bases with Piperazine Moiety.

A series of novel Mannich bases were designed, synthesized, and screened for their antimicrobial activity. The target compounds were synthesized from 4-(3-chlorophenyl)-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and different piperazine derivatives. The structures of the products were confirmed by 1H and 13C NMR and elemental analysis. The activity of piperazine derivatives against bacteria (Gram-positive: Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus, Bacillus cereus, and Bacillus subtilis; Gram-negative: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis) and yeasts (Candida glabrata, Candida krusei, and Candida parapsilosis) was determined by the minimum inhibitory concentration and minimum bactericidal concentration values. Significant activity was observed against Gram-positive bacteria, mainly staphylococci (PG7-PG8) and bacteria of the genes of Micrococcus and Bacillus (PG1-3), as well as selected strains of Gram-negative bacteria, including bacteria of the Enterobacteriaceae family (PG7), while all tested compounds showed high fungistatic activity against Candida spp. yeasts, especially C. parapsilosis, with MICs ranging from 0.49 µg/mL (PG7) to 0.98 µg/mL (PG8) and 62.5 µg/mL (PG1-3). In conclusion, the results obtained confirm the multidirectional antimicrobial activity of the newly synthesized piperazine derivatives. Furthermore, in silico studies suggest that the tested compounds are likely to have good oral bioavailability. The results obtained will provide valuable data for further research into this interesting group of compounds. The library of compounds obtained is still the subject of pharmacological research aimed at finding new interesting biologically active compounds.

Fungistatic Effect of Phthalide Lactones on Rhodotorula mucilaginosa.

Currently, there is an increasing number of cases of fungal infections caused by opportunistic strains of the yeast Rhodotorula mucilaginosa, mainly in immunocompromised patients during hospitalization. The excessive use of antibiotics and azole compounds increases the risk of resistance to microorganisms. A new alternative to these drugs may be synthetic phthalide lactones with a structure identical to or similar to the natural ones found in celery plants, which show low toxicity and relatively high fungistatic activity. In the present study, the fungistatic activity of seven phthalide lactones was determined against R. mucilaginosa IHEM 18459. We showed that 3-n-butylidenephthalide, the most potent compound selected in the microdilution test, caused a dose-dependent decrease in dry yeast biomass. Phthalide accumulated in yeast cells and contributed to an increase in reactive oxygen species content. The synergistic effect of fluconazole resulted in a reduction in the azole concentration required for yeast inhibition. We observed changes in the color of the yeast cultures; thus, we conducted experiments to prove that the carotenoid profile was altered. The addition of lactones also triggered a decline in fatty acid methyl esters.

Alternative Functionalization of 2‐(3,4‐Dihalophenyl)‐4H‐chromen‐4‐ones via Metal‐Free Nucleophilic Aromatic Fluorine Substitution and Palladium‐Catalyzed Cross‐Coupling Reactions

AbstractAlternative pathways for the functionalization of 2‐(3‐bromo‐4‐fluorophenyl)‐ and 2‐(3,4‐difluorophenyl)‐4H‐chromen‐4‐ones have been studied under conditions of metal‐free base‐promoted nucleophilic aromatic substitution and palladium‐catalyzed Suzuki‐Miyaura cross‐coupling reaction. The possibility of implementing these two synthetic techniques is shown by the example of obtaining 2‐[3‐aryl‐4‐(1H‐azol‐1‐yl) phenyl]‐4H‐chromen‐4‐ones. Evaluation of the antimicrobial effect of the synthesized azolyl‐substituted flavones was carried out. Compounds with moderate anti‐influenza, anti‐gonococcal and high fungistatic activity were found.

Rola olejków eterycznych w terapii grzybicy skóry i jej przydatków

Skin diseases are not only a health problem, but also a significant psychological and social trouble affecting every age group of patients. One of the largest groups of skin diseases are mycoses including mycoses of the skin and its appendages. The most common symptoms of infection are skin itching and burning, followed by disruption at the stratum corneum. Treatment includes the use of natural antibiotics such as griseofulvin and synthetic derivatives such as terbinafine. Chronic skin disease, which includes mycosis, necessitates taking medications for a long time, which translates into reduced effectiveness of the drug and side effects. The latest results of study herbal substances prove that they exhibit high fungistatic and fungicidal activity. Therefore, medicinal plants and their secondary metabolites are increasingly used in antifungal therapy. Essential oils are one of the products of secondary metabolism of plants. With the right dosage, they can be used for a long time with eliminating the risk of side effects. So far have been no reports of the increasing resistance of bacterial or fungal strains to the components of essential oils, which often occur in the case of long-term antibiotic therapy. The paper describes essential oils of tea tree, thyme, oregano, basil, sage, savory, clove and cinnamon, showing the greatest effectiveness in the antifungal therapy of the skin and its appendages.

Biological activity of compositions of nonmetal nanoparticles

Biological activity of compositions of nonmetal nanoparticles I+S and Se+I has been studied. Composition of nanoparticles I+S was shown to exhibit high antiviral activity against PTV-1 strain Dniprovskyi 34, decreasing its titer by 5,0 lg TCD50/cm3 and having therapeutic index 8. The antiviral activity is the most prominent according to the virucidal plot of study and is dose dependent. The result is significant according to Student’s t-test. Composition of Se+I NPs exhibited high fungistatic activity against strain A. cucurbitacearum 502 during the whole term of cultivation. Reduction in colony diameters under the influence of composition of Se+I NPs was up to 94.13% and the difference revealed to have high level of significance according to statistical tests. According to the results of the study, composition of I+S NPs can be recommended for the development of antiviral drugs, virucidal agents and disinfectants, whereas composition of Se+I NPs can be recommended for the creation of substances to protect agricultural plants from fungal diseases.

PHYTONCIDAL ACTIVITY OF ESSENTIAL OILS OF MEDICINAL PLANTS TO SOME STRAINS OF MOLD FUNGI

Herbal antiseptics with phytoncidal action, for example, plant essential oils, can be used indoors in the presence of people. The antifungal activity of essential oils of medicinal plants (anis, basil, clary cage, clove, coriander, jasmine, juniper, lavender, lemon, orchid, rose, rosemary, tea tree, wormwood, ylang ylang) was evaluated by the degree of growth inhibition of mold colonies Alternaria alternata , Aspergillus oryzae, Aspergillus flavus, and Cladosporium cladosporioides. Colonies incubated in Petri dishes with a drop of essential oil on the lid under control petrolatum. All essential oils in the experiment had phytoncidal properties. The oils were divided into groups: 1 with fungicidal action (coriander, jasmine, orchid, rose); 2 with high fungistatic activity to all strains (lavender, basil, tea tree oil); 3 with fungistatic properties against individual strains (C. cladosporioides rosemary and anise, A. alternata and A. flavus lemon, A. oryzae wormwood); 4 with a stimulating effect of the growth of colonies A. oryzae lemon oil.

Active chemical fractions with high fungistatic activity of humic‐like substances obtained via different extraction solvents

AbstractBACKGROUNDHumic‐like substances (HULIS) for use in controlling soil‐borne diseases have been a research focus, but obtaining HULIS with high fungistatic activity via different extraction solvents has been challenging. In this work, three solvents were selected to extract HULIS from weathered coal. Inhibition rates against phytopathogens were used to evaluate the fungistatic activities of HULIS. Element contents (C, N, S, and O) and carbon‐13‐cross polarization magic‐angle spinning nuclear magnetic resonance (13C‐CP‐MAS NMR) spectra were used to evaluate the chemical composition. The relationships between the chemical compositions and fungistatic activities were assessed by redundancy analysis (RDA) and partial least squares regression (PLSR).RESULTSThe results showed that HULIS extracted with different solvents varied in the element contents, organic carbon structures and fungistatic activities. HULIS extracted with potassium hydroxide–ethanol had the highest content of C, the lowest contents of N and O, and the highest fungistatic activities (up to 71.86%). Consistent results through RDA and PLSR shows that C and S had positive effects on the fungistatic activity, while N and O had negative effects. Aliphatic C in HULIS had positive effects on the fungistatic activity, while the aromatic fraction and anomeric C had negative effects.CONCLUSIONIn summary, different solvents extracted different fractions from weather coal. Mixed solvents with organic and inorganic solvents were more beneficial for extracting active fractions with higher fungistatic activity of HULIS from weather coal. The results of this work provide a good theoretical basis for the application of HULIS extracted from weathered coal. © 2019 Society of Chemical Industry

Antifungal activity of extracts, essential oil and constituents from Petroselinum crispum against Colletotrichum acutatum

Se evaluó el efecto de extractos, el aceite esencial y los componentes principales del perejil (Petroselinum crispum (Mill.) Fuss.) contra el hongo fitopatógeno Collectotrichum acutatum mediante el método del agar envenenado. Los resultados mostraron que todos los extractos, junto con elaceite esencial, inhibieron significativamente el crecimiento radial de C. acutatum en concentraciones superiores a 100 μg mL-1. La mayor actividad se encontró para el aceite esencial, seguido por el extracto de n-hexano. El análisis por cromatografía de gases con espectroscopia de masas (CG-EM)del extracto de n-hexano y el aceite esencial de P. crispum mostró que los componentes principales corresponden a los fenilpropanoides miristicina y parsley-apiol. Ambos compuestos fueron aislaron por técnicas cromatográficas convencionales y sus estructuras elucidadas por métodos espectroscópicos. La miristicina y el parsley-apiol mostraron un efecto inhibidor significativo contra C. acutatum. La actividad fungistática más alta se encontró para parsley-apiol con un valor CI50 de 40 μg mL-1. Enconclusión, el perejil puede ser una buena fuente de compuestos antimicóticos para controlar el C. acutatum.

In vitro fungistatic activity of 36 traditional oriental medicines and their synergistic effect against Trichophyton rubrume

Objective: To investigate the fungistatic activity and synergistic effects of natural products and their constituents, including traditional oriental medicines (TOMs). Methods: Fungistatic activities of TOMs prepared by hot-water (115 °C) or ethanol (70%; 40 °C) extraction were determined by their minimum inhibitory concentration. To assess possible synergistic effects, minimum inhibitory concentrations of various combinations were evaluated. Results: By evaluating antifungal susceptibility of Trichophyton rubrum, which is a major causative fungus for several types of dermatophytosis, we confirmed that ethanol extracts were more active than hot-water extracts in 25 of the 36 TOMs, suggesting that the constituents with high hydrophobicity tend to contribute significantly to fungistatic activity. We selected four TOMs with high fungistatic activity, including Aucklandiae radix, Gentianae macrophyllae radix, Scutellariae radix, and Galla rhois, and their synergistic effects were investigated through the combination studies between TOMs or TOM-conventional drug terbinafine. In combinations between four TOMs, partial synergistic effects were observed in Aucklandiae radix–Galla rhois and Gentianae macrophyllae radix–Galla rhois combinations, as supported by the lowest fractional inhibitory concentration index value of 0.66 for both combinations. Furthermore, Galla rhois showed the strongest synergistic effect on growth inhibition of Trichophyton rubrum with a fractional inhibitory concentration index value of 0.50 in combination with terbinafine. Conclusions: Our findings indicate that the combination of TOMs and TOM-terbinafine may be effective on treatment for chronic and recurrent dermatophytosis by improving fungistatic activity and led to decrease systemic toxicity in clinical practice.

Synthesis and fungistatic activity of bicyclic lactones and lactams against Botrytis cinerea, Penicillium citrinum, and Aspergillus glaucus.

Six analogues of natural trans-4-butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and three derivatives, 11, 12, and 13, of Vince lactam (10) were synthesized and tested as fungistatic agents against Botrytis cinerea AM235, Penicillium citrinum AM354, and six strains of Aspergillus. Moreover, bioresolution carried out by means of whole cell microorganisms and commercially available enzymes afforded opposite enantiomerically enriched (-) and (+) isomers of Vince lactam (10), respectively. The effect of compound structures and stereogenic centers on biological activity has been discussed. The highest fungistatic activity was observed for four lactones: 3, 4, 7, and 8 (IC50 = 104.6-115.2 μg/mL) toward B. cinerea AM235. cis-5,6-Epoxy-2-aza[2.2.1]heptan-3-one (13) indicated significant fungistatic activity (IC50 = 107.1 μg/mL) against Aspergillus glaucus AM211. trans-4-Butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and trans-4-butyl-cis-3-oxabicyclo[4.3.0]non-7-en-2-one (7) exhibited high fungistatic activity (IC50 = 143.2 and 110.2 μg/mL, respectively) against P. citrinum AM354 as well.

Antifungal activity of oligochitosans (short chain chitosans) against some Candida species and clinical isolates of Candida albicans: Molecular weight–activity relationship

A series of oligochitosans (short chain chitosans) prepared by acidic hydrolysis of chitosan and characterized by their molecular weight, polydispersity and degree of deacetylation were used to determine their anticandidal activities. This study has demonstrated that oligochitosans show a high fungistatic activity (MIC 8–512 μg/ml) against Candida species and clinical isolates of Candida albicans, which are resistant to a series of classic antibiotics. Flow cytometry analysis showed that oligochitosan possessed a high fungicidal activity as well. For the first time it was shown that even sub-MIC oligochitosan concentration suppressed the formation of C. albicans hyphal structures, cause severe cell wall alterations, and altered internal cell structure. These results indicate that oligochitosan should be considered as a possible alternative/additive to known anti-yeast agents in pharmaceutical compositions.

Research on possibilities of utilization of chosen Brassicaceae plants in protection of cucumber against damping-off caused by Rhizoctonia solani Kühn and Fusarium culmorum (W.G.Smith)Sacc.

The aim of the work was to determine the usefulness of dried leaves of savoy cabbage, red cabbage, horse radish and fringed cabbage in protection of cucumber against damping-off caused by fungi <i>Rhizoctonia solani</i> and <i>Fusarium culmorum</i>. In the laboratory experiments, pathogens were grown on PDA containing dried leaves (3g·100 cm<sup>-3</sup>) and in atmosphere containing volatile substances evolved from plant material. The addition of radish horse leaves into PDA caused total inhibition of <i>R. solani</i> development. Remaining plants were also characterized by high fungistatic activity (% of growth inhibition about 85%). <i>F. culmorum</i> was less sensitive. The horse radish leaves showed the strongest activity (65 %), weakest in combination with fringed cabbage leaves (38,9%). The similar regularity in the case of fumigation activity was observed. The effectiveness of dried leaves in protection of cucumber against damping-off was confirmed in greenhouse experiment. The amendment of soil inoculated with <i>R. solani</i> in dose 2 g per 500 cm<sup>3</sup> of soil significantly increased the number of cucumber sprouts compared to the control. In the experiment with <i>F. culmorum</i> only in combination with horse radish and red cabbage leaves significant action was observed.

Fungistatic Activity of Bicyclo[4.3.0]-γ-lactones

Five optically active and sixteen racemic lactones (nine of them new) of bicyclo[4.3.0]nonane structure were synthesized. IC(50) values for the following phytopathogens were determined: Aspergillus ochraceus AM 456, Fusarium culmorum AM 282, Fusarium oxysporum AM 13, Fusarium tricinctum AM 16. Effect of compound structures, especially stereogenic centers, on fungistatic activity has been discussed. The highest fungistatic activity was observed for trans-7,8-dibromo-cis-3-oxabicyclo[4.3.0]nonan-2-one (3c), IC(50) = 30.1 μg/mL (0.10 μM/mL), and cis-7,8-epoxy-cis-3-oxabicyclo[4.3.0]nonan-2-one (3b), IC(50) = 72.2 μg/mL (0.47 μM/mL), toward F. oxysporum AM 13.

Antimicrobial Activity of Undecan-x-Ones (x = 2-4)

As a continuation of our research on the biological activity of undecan-x-ones (x = 2-4), their antimicrobial activity towards bacteria Escherichia coli and Bacillus subtilis, yeast Candida mycoderma and mould Aspergillus niger, was investigated. The population viability of the tested microbial strains in the presence of undecan-x-ones was determined by the impedimetric and agar disc diffusion methods. Undecan-x-ones showed low antibacterial activity towards both Gram-positive and Gram-negative bacteria. Undecan-2-one and undecan-3-one exhibited high activity towards C. mycoderma. All undecan-x-ones expressed the strongest effect on A. niger. The tests have proven that due to high fungistatic activity undecan-x-ones can be used to aid stabilization of food and cosmetic matrices.

Fungitoxicity of Lippia scaberrima essential oil and selected terpenoid components on two mango postharvest spoilage pathogens

Lippia scaberrima, an aromatic shrub with medicinal properties, is indigenous to southern Africa. Essential oil obtained from aerial plant parts was assessed in vitro and in vivo for antifungal activity against Botryosphaeria parva and Colletotrichum gloeosporioides isolated from mango fruit. Exposure to oil vapour for 2 and 4 days caused inhibition of mycelial growth of both isolates. Three major terpenoids identified in the oil, limonene, R-(−)-carvone, and 1,8-cineole, as well as S-(+)-carvone, were individually evaluated in vitro. The two enantiomers of carvone, along with L. scaberrima oil, were found to have the highest fungistatic activity. Oil and carvone enantiomer fungicidal activities were less pronounced. The use of commercial wax coatings enriched with essential oils led to reduced fungal infection by both pathogens. Results of the in vitro and preliminary in vivo studies suggest that employing L. scaberrima oil to control postharvest pathogens is worthy of further investigation.

Synthesis and in vitro antifungal activity of 1-amino-3,4-dialkylnaphthalene-2-carbonitriles and their analogues.

Twenty-four 3- and/or 4-alkyl-substituted 1-aminonaphthalene-2-carbonitriles and their analogues were prepared and evaluated for growth-inhibiting activity against four phytopathogenic fungi: Fusarium culmorum, Alternaria brassicicola, Botrytis cinerea and Penicillium expansum. The results obtained were compared with the activity of a commercial fungicide. The highest fungistatic activity was revealed by amino nitriles having hydrogen atoms or only one short alkyl group (CH3, C2H5) at the 3- or 4-position of the naphthalene system. The minimum values of calculated EC50 and EC95 indexes were 1.1 and 5.1 mg litre-1, respectively. These values were considerably lower than those for the reference fungicide.

Dimethylheptyl [3‐(N‐hetaryl)propyl]silanes: Synthesis, antimicrobial and antiblastic activity

AbstractThe alkylation of monoazoles, diazoles, triazoles and tetrazoles with dimethylheptyl(3‐iodopropyl)silane using liquid/liquid phase‐transfer catalysis affords the corresponding [3‐(N‐azolyl)propyl]silanes in high yield, by which means the nonsymmetric ambident heterocycles 1,2,4‐triazole and tetrazole undergo alkylation regiospecifically in position 1 and 2, respectively. Dimethylheptyl[3‐(N‐imidazolyl)propyl]silane demonstrated high fungistatic activity with respect to S. cerevisiae and T.rubrum in combination with high cytotoxicity.

Fungistatic activity of different Indian soils againstFusarium udum Butler

The fungistatic activity of different Indian soils againstF. udum, causing wilt disease of pigeon-pea, has been assessed in relation to soil pH and organic matter. Correlation co-efficient between soil characteristics and fungistasis has been calculated to evaluate relationship. High fungistatic activity was exhibited generally by the soils having low pH but high organic matter. The soils exhibiting high fungistatic activity againstF. udum have low incidence of wilt disease of pigeon-pea. There was no definite correlation between volatile and non-volatile fungistasis and, therefore, the origins of volatile and non-volatile fungistasis are different. In the usual biological limit pH had insignificant impact on fungistasis.

THE FUNGISTATIC ACTIVITY OF ETHYLENIC AND ACETYLENIC COMPOUNDS III. THE FUNGISTATIC ACTIVITY OF TETRAIODOETHYLENE AND RELATED COMPOUNDS

The high fungistatic activity of tetraiodoethylene has been investigated. Diiodo‐acetylene, which like tetraiodoethylene is an unsaturated substance containing only carbon and iodine, has also been found to have a high antifungal action. The effect of replacing the iodine atoms in these compounds by hydrogen, bromine, and carboxyl and nitro groups has been studied. The high fungistatic activity of some iodoethylenic and iodoacetylenic compounds appears to be associated with the presence in the molecule of positive iodine.

Viridin: a Highly Fungistatic Substance Produced by Trichoderma viride

THE mould Trichoderma viride Pers. ex Fries is generally known to possess marked powers of antagonism to other fungi. It has been previously shown1 that some strains of this mould produce gliotoxin. We have recently found a number of strains which produce another substance, which we propose to name 'viridin', characterized by remarkably high fungistatic activity.