Anticandidal activity of Cassia fistula and its effect on ergosterol biosynthesis

Context:?Cassia fistula Linn. (Caesalpiniaceae) has been used in folk medicine. Anthraquinone derivative rhein having antimicrobial properties is actively present in C. fistula fruit. Although, as yet there has been no study of its anticandidal potential.

Objective:?The present study was conducted to determine the phytochemical composition of fruit pulp and seed extract and their effect on Candida albicans ATCC 10261, Candida glabrata ATCC 90030 and Candida tropicalis ATCC 750, respectively.

Materials and methods:?The fruit pulp and seed extracts were tested for phytochemicals by various standard methods and rhein was identified by thin-layer chromatography. The anticandidal activity was determined by minimum inhibitory concentration (MIC), growth curve studies, cytotoxicity and ergosterol estimation assay.

Results:?The fruit pulp and seed extracts showed high content of phenolic compounds. Rhein was identified in both extracts, Rf 0.38. MICs of seed extract obtained with C. albicans, C. tropicalis and C. glabrata is 350, 300 and 300?μg/ml. However, for fruit pulp extract, these values significantly reduced to 150, 250 and 100?μg/ml, respectively. Comparative MIC values for fluconazole were 16, 16 and 04 µg/ml. At MICs, pulp reduced ergosterol content in cell membrane of C. albicans, C. tropicalis and C. glabrata by 54.42, 48.78 and 68.0%, seed extract by 38.11, 47.0 and 45.0%, whereas, fluconazole showed 93.56, 89.21 and 98.0%, respectively.

Discussion and conclusion:?C. fistula fruit pulp and seed extract possessed anticandidal activity. The result was significantly correlated between the MICs, cytotoxicity and ergosterol inhibition. It was concluded that the crude extract is a promising source for anticandidal compounds.     

Microbial conversion and anticandidal effects of bioconverted product of cabbage (Brassica oleracea) by Pectobacterium carotovorum pv. carotovorum 21

This study was undertaken to examine the anticandidal effects of microbially bioconverted product of cabbage, obtained from the microbial conversion of cabbage (Brassica oleracea var. capitata) by a bacterial strain Pectobacterium carotovorum pv. carotovorum 21 (Pcc 21) against various isolates of Candida species including a clinical isolate. The bioconverted product (10 μl, corresponding to 500 μg/disc) displayed potential anticandidal effect against Candida albicans KACC 30062, Candida geochares KACC 30061, Candida albicans KACC 30003, Candida saitoana KACC 41238 and Candida glabrata P00368 (clinical isolate) as a diameter of zones of inhibition, found in the range of 14 ± 0.9 to 19 ± 1.1 mm. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of bioconverted product against the tested isolates were found in the range of 62.5–250 and 125–250 μg/ml, respectively. Also the bioconverted product had remarkable anticandidal effect on the viable counts of the tested Candida isolates. Further, scanning electron microscopic study revealed potential detrimental effect of bioconverted product on the morphology of C. albicans KACC 30062 at MIC concentration. All these findings together indicate that bioconverted product of cabbage has potential therapeutic value of medicinal significance to control Candida species including clinical isolates.     

Antifungal activity and potential mechanism of action of caspofungin in combination with ribavirin against Candida albicans

The number of invasive fungal infections has increased dramatically, resulting in high morbidity and mortality among immunocompromised patients. With increasing use of caspofungin (CAS), resistant strains have emerged frequently and led to limitations in the treatment of patients with severe invasive Candida albicans infections. Combination therapy is an important method to deal with this issue. As such, this study investigated the activity of CAS in combination with ribavirin (RBV) against C. albicans. The results of this in-vitro study showed that the minimum inhibitory concentrations (MICs) of CAS and RBV when they were used as monotherapy were 0.5–1 μg/mL and 2–8 μg/mL, respectively, while the MIC of CAS decreased from 0.5–1 μg/mL to 0.0625–0.25 μg/mL when used in combination with RBV, with a fractional inhibitory concentration index (FICI) ≤0.5. In addition, the RBV + CAS combination group displayed synergistic effects against C. albicans biofilm over 4 h; the sessile MIC (sMIC) of CAS decreased from 0.5–1 µg/mL to 0.0625–0.25µg/mL and the sMIC of RBV decreased from 4–16 µg/mL to 1–2 µg/mL, with FICI <0.5. The survival of C. albicans-infected Galleria mellonella was prolonged, the fungal burden was decreased, and the area of tissue damage was reduced after combination therapy. Further study showed that the mechanisms of action of the synergistic effect were related to the inhibition of biofilm formation, the inhibition of hyphal growth, and the activation of metacaspases, but were not related to the accumulation of reactive oxygen species. It is hoped that these findings will contribute to the understanding of drug resistance in C. albicans, and provide new insights for the application of RBV.     

Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution,clinical features and antifungal susceptibilities

Candida spp. are among the most frequent nosocomial pathogens, contributing significantly to morbidity and mortality. Longitudinal data on the epidemiology of Candida bloodstream infections (BSIs) are still limited. Isolates and clinical data from 1218 episodes of Candida BSI were prospectively collected from patients in 52 hospitals in the USA between 1998 and 2006. Susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, voriconazole, anidulafungin, caspofungin and micafungin were determined for 1077 Candida isolates by the CLSI reference broth microdilution method using the recently published species-specific clinical breakpoints. Candida albicans was the most prevalent species (50.7%), followed by Candida parapsilosis (17.4%), Candida glabrata (16.7%) and Candida tropicalis (10.2%). The prevalence of non-albicans Candida spp. increased over time. Patients had a mean age of 51 years and a mean length of hospital stay prior to BSI of 22 days. The main underlying conditions were gastrointestinal (20.1%) and pulmonary (13.0%) diseases. Intravenous catheters (19.1%) and the urinary tract (8.0%) were the most frequently determined likely sources, whilst in the majority of patients (61.1%) no source could be identified. Overall mortality was 38.1%. Of the isolates studied, 0.8% of C. albicans, 100.0% of C. glabrata, 2.9% of C. parapsilosis and 4.9% of C. tropicalis were non-susceptible to fluconazole, and 0.6% of C. albicans, 5.0% of Candida krusei, 7.6% of C. parapsilosis and 9.8% of C. tropicalis were non-susceptible to voriconazole. All echinocandins showed good activity against most Candida spp., including the majority of C. parapsilosis isolates, but only 38.1% of C. glabrata tested susceptible to caspofungin.     

Antifungal activity of ribavirin used alone or in combination with fluconazole against Candida albicans is mediated by reduced virulence

The incidence of fungal infections has increased continuously in recent years, and drug resistance, especially resistance to fluconazole (FLC), has emerged. To overcome this challenge, research on the antifungal activities of non-antifungal agents has gained more attention. In this study, we determined the anti-Candida activity of ribavirin (RBV), an antiviral drug commonly used in the clinic, and found that RBV displayed potent antifungal activity when used alone or in combination with FLC in vitro and in vivo. In vitro, the MIC₈₀ values of RBV were 2–4 µg/mL for FLC-susceptible Candida albicans and 8 µg/mL for FLC-resistant C. albicans. When RBV at a dose of 1 µg/mL was combined with FLC, significant synergistic effects were exhibited against FLC-resistant C. albicans, and the MICs of FLC decreased from >512 µg/mL to 0.25–1 µg/mL. Synergism was also exhibited against C. albicans biofilms. In vivo, RBV plus FLC significantly improved the survival of infected Galleria mellonella larvae compared with the FLC-treated group over a 4-day period and attenuated the damage of FLC-resistant C. albicans to G. mellonella larvae tissue. Furthermore, mechanistic studies indicated that the antifungal effects of RBV used alone or in combination with FLC might be associated with inhibition of biofilm formation, reduced extracellular phospholipase activity and inhibition of hyphal growth, but is not related to promotion of FLC uptake and inhibition of FLC efflux. These results provide a promising direction for overcoming drug resistance and for expanding the clinical application of existing drugs.     

Synergic effect of combination of glycyrol and fluconazole against experimental cutaneous candidiasis due to <Emphasis Type="Italic">Candida albicans</Emphasis>

In this study, we investigated the anti-fungal activity of glycyrol, a coumarine isolated from licorice (Glycyrrhizae Radix), in a murine model of cutaneous candidiasis caused by Candida albicans. Compared to the infected sites, located on the mice’s back, of the untreated control mice, the infected sites treated with glycyrol had reduced CFU (colony forming unit) values up to 60 and 85.5 % at 20 and 40 μg/mouse of glycyrol, respectively (P < 0.01). The antifungal activity of glycyrol was synergistically increased when glycyrol (10 μg/mouse) was combined with fluconazole (10 μg/mouse), demonstrating that the combination therapy is approximately 4 times more effective than fluconazole alone at 20 μg/mouse (P < 0.01). Additionally, the combination activity was 1.65 times greater than the antifungal activity of fluconazole alone at 40 μg/mouse (P < 0.05). In seeking glycyrol’s antifungal mechanism, we determined that glycyrol inhibited hyphal induction and cell wall adherence of C. albicans. Thus, it is very likely that, by damaging the cell wall, glycyrol helps fluconazole invade C. albicans more readily and attack fluconazole’s target in the fungus membrane. In summary, our data indicate that glycyrol may contribute to the development of a novel agent that possesses antifungal activity against cutaneous candidiasis.     

Diverse role of microbially bioconverted product of cabbage (Brassicaoleracea) by Pseudomonassyringe pv. T1 on inhibiting Candida species

This study was carried out to evaluate the anticandidal effects of bioconverted product, obtained from the microbial conversion of cabbage (Brassicaoleracea) by a bacterial strain Pseudomonassyringe pv. T1 (Ps-T1) against various isolates of Candida species. The diameters of zones of inhibition of bioconverted product of cabbage (10 μl, corresponding to 500 μg/disc) against Candidaalbicans KACC 30003 and 30062, Candidageochares KACC 30061, Candidasaitoana KACC 41238 and Candidaglabrata P00368 were found between 10 ± 1 and 16 ± 0.8 mm. The bioconverted product was tested for the minimum inhibitory and minimum fungicidal concentration values against the tested pathogens which were found in the range of 125-500 and 125-500 μg/ml, respectively. On the viable counts of the tested fungal pathogens, the bioconverted product showed a remarkable anticandidal effect. Also the study of using scanning electron microscopy on the morphology of C.albicans KACC 30062 revealed potential detrimental effect of bioconverted product at MIC concentration. The results of this study suggest that bioconverted product of cabbage by Ps-T1 holds potential therapeutic value and medicinal significance to control Candida species.     

Colistin interacts synergistically with echinocandins against Candida auris

Antifungal combination is an interesting approach for the treatment of several fungal infections but there is currently little evidence to support combined therapy in Candida auris infections. The antibacterial colistin has recently been shown to interact synergistically with antifungals against Candida spp., including azole-resistant isolates. The current study evaluated the in vitro interaction between colistin and either caspofungin or micafungin against 15 C. auris isolates by a checkerboard methodology based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method. Results were analysed by two approaches: calculation of the fractional inhibitory concentration index (FICI) and response surface analysis based on the Bliss model. The minimum inhibitory concentration (MIC) range (geometric mean [Gmean]) of caspofungin and micafungin was 0.25 to 1 µg/mL (0.691 µg/mL) and 0.03 to 0.125 µg/mL (0.114 µg/mL), respectively. No activity was observed for colistin alone with MIC of >64 µg/mL for all the isolates. When colistin was combined with caspofungin, synergistic interactions were observed for all strains with FICI values of 0.08 to 0.14. In contrast, indifferent interactions were observed for the combination of colistin with micafungin with FICI values of 0.51 to 1.01. Synergy was also demonstrated using the Bliss model against all isolates for the colistin-caspofungin combination and in 60% of isolates for the colistin-micafungin combination. Antagonism was not observed for any combination.     

Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008-2009)

Minimum inhibitory concentration (MIC) data from the SENTRY Antimicrobial Surveillance Program generated by reference methods were analysed to compare the antifungal resistance profiles and species distribution of Candida bloodstream infection (BSI) isolates obtained from patients in the Intensive Care Unit (ICU) and those from non-ICU locations. Results from 79 medical centres between 2008 and 2009 were tabulated. MIC values were obtained for anidulafungin, caspofungin, micafungin, fluconazole, posaconazole and voriconazole. Recently revised Clinical and Laboratory Standards Institute breakpoints for resistance were employed. A total of 1752 isolates of Candida spp. were obtained from ICU (779; 44.5%) and non-ICU (973; 55.5%) settings. The frequency of ICU-associated Candida BSI was higher in Latin America (56.5%) compared with Europe (44.4%) and North America (39.6%). The frequency of candidaemia in the ICU decreased both in Latin America and North America over the 2-year study period. Approximately 96% of isolates both in ICU and non-ICU settings were caused by only five species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei). Resistance both to azoles and echinocandins was uncommon in ICU and non-ICU settings. Overall, fluconazole resistance was detected in 5.0% of ICU isolates and 4.4% of non-ICU isolates. Candida glabrata was the only species in which resistance to azoles and echinocandins was noted, and this multidrug-resistant phenotype was found in both settings. In conclusion, the findings from this global survey indicate that invasive candidiasis can no longer be considered to be just an ICU-related infection, and efforts to design preventive and diagnostic strategies must be expanded to include other at-risk populations and hospital environments. Concern regarding C. glabrata must now include resistance to echinocandins as well as azole antifungal agents.     

Antimicrobial activity of Buchenavia tetraphylla against Candida albicans strains isolated from vaginal secretions

Context: Buchenavia tetraphylla (Aubl.) RA Howard (Combretaceae: Combretoideae) is an ethnomedicinal plant with reported antifungal action.

Objective: This study evaluates the antimicrobial activity of B. tetraphylla leaf extracts against clinical isolates of Candida albicans. The morphological alterations, combinatory effects with fluconazole and the cytotoxicity of the active extract were analyzed.

Materials and methods: Extracts were obtained using different solvents (hexane: BTHE; chloroform: BTCE; ethyl acetate: BTEE; and methanol: BTME). Antimicrobial activity was determined by the broth microdilution method using nine strains of C. albicans isolated from vaginal secretions and one standard strain (UFPEDA 1007).

Results: All extracts showed anti-C. albicans activity, including against the azole-resistant strains. The MIC values ranged from 156 to 2500?μg/mL for the BTHE; 156 to 1250?μg/mL for the BTCE; 625 to 1250?μg/mL for the BTME and 625?μg/mL to 2500?μg/mL for the BTEE. BTME showed the best anti-C. albicans activity. This extract demonstrated additive/synergistic interactions with fluconazole. Scanning electron microscopy analysis suggested that the BTME interferes with the cell division and development of C. albicans. BTME showed IC₅₀ values of 981 and 3935?μg/mL, against J774 macrophages and human erythrocytes, respectively. This extract also enhanced the production of nitric oxide by J774 macrophages.

Discussion and conclusion: Buchenavia tetraphylla methanolic extract (BTME) is a great source of antimicrobial compounds that are able to enhance the action of fluconazole against different C. albicans strains; this action seems related to inhibition of cell division.     

Screening of in vitro antimicrobial activity of plants used in traditional Indonesian medicine

Context: In many regions of Indonesia, there are numerous traditional herbal preparations for treatment of infectious diseases. However, their antimicrobial potential has been poorly studied by modern laboratory methods.

Objective: This study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37 plant species used in Indonesian traditional medicine for treatment against Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

Materials and methods: The plants were collected from the Biopharmaca collection garden, Bogor, Indonesia. The plant material was dried, finely grounded, extracted using ethanol, concentrated, and the dried residue was dissolved in 100% DMSO. Antimicrobial activity was determined in terms of a minimum inhibitory concentration (MIC) using a broth microdilution method in 96-well microplates.

Results: The extract of Orthosiphon aristatus (Blume) Miq. (Lamiaceae) leaf produced the strongest antimicrobial effect, inhibiting the growth of C. albicans (MIC 128?μg/mL), S. aureus (MIC 256?μg/mL), E. faecalis (MIC 256?μg/mL) and P. aeruginosa (MIC 256?μg/mL). The leaf extract of Woodfordia floribunda Salisb. (Lythraceae) also exhibited significant effect against C. albicans (MIC 128?μg/mL), S. aureus (MIC 256?μg/mL) and E. faecalis (MIC 256?μg/mL). Rotheca serrata (L.) Steane &; Mabb. (Lamiaceae) leaf extract inhibited the growth of S. aureus (MIC 256 µg/mL) and C. albicans (MIC 256 µg/mL).

Discussion and conclusions: The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect. Therefore, both of these plants can serve as prospective source materials for the development of new anti-candidal agents.     

In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates

Context: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance.

Objectives: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated.

Materials and methods: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis.

Results: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0?μg/mL) and WIF and FLZ (1.95:8.0?μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700–800?cm^?1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF.

Conclusions: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat’s claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.     

The effects of Ficus carica on the activity of enzymes related to metabolic syndrome

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67 ± 5.51 μg/mL and 81.67 ± 4.00 μg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p < 0.05) higher than all other extracts and parts of the plant in terms of antioxidative, antidiabetic, and antiobesogenic effects. The IC₅₀ values of the fruit ethanolic extract in terms of antioxidative (134.44 ± 18.43 μg/mL), and inhibition of α-glucosidase (255.57 ± 36.46 μg/mL), α-amylase (315.89 ± 3.83 μg/mL), and pancreatic lipase (230.475 ± 9.65 μg/mL) activity indicate that the activity of fruit ethanolic extract is better than all other extracts of the plant. The gas chromatography–mass spectroscopy analysis of the fruit ethanolic extract showed the presence of a number of bioactive compounds such as butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. The results of this study suggest that the ethanolic extract of the fruit of F. carica may have potential antidiabetic and antiobesogenic agents.     

Synthesis, antimicrobial and cytotoxic activities of novel 4-trifluoromethyl-(1,2,3)-thiadiazolo-5-carboxylic acid hydrazide Schiff’s bases

A series of novel 1,2,3-thiadiazolo-5-carboxylic acid hydrazide Schiff’s bases 4a–4r were prepared starting from ethyl-4,4,4-trifluoroacetoacetate and ethyl carbazate in four steps. All the compounds were screened for antibacterial activity against various bacterial strains at 150 μg/ml concentration and found no activity. Similarly, all the compounds were screened for antifungal activity against various fungal strains at 100 and 150 μg/ml concentrations. Compounds 4a, 4m, and 4q found to show moderate activity against Candida albicans. Further, compounds were evaluated for cytotoxic activity against breast carcinoma cells MDA-MB 231 (aggressive), MCF-7 (non-aggressive) using doxorubicin as standard. Compound 4n was found to show 25.39 % cell viability against MDA-MB 231 and 63.60 % cell viability against MCF-7 cells.     

Echinocandin antifungal drugs in fungal infections: a comparison

This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed echinocandins: caspofungin, micafungin and anidulafungin. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections. The echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including azole-resistant pathogens. For all agents, strains with drug minimum inhibitory concentrations (MICs) of ≤ 2?μg/mL are considered susceptible; the MIC at which 90% of isolates tested were inhibited (MIC??) values are typically <2?μg/mL but 100-fold higher MIC?? values are seen with Candida parapsilosis (1-2?μg/mL) and Candida guilliermondii (1-4?μg/mL). Activity is comparable between the three agents, although limited data indicate that anidulafungin may have low MICs against C. parapsilosis and Candida glabrata strains that demonstrate elevated MICs to caspofungin and micafungin. All three drugs have good fungistatic activity against Aspergillus spp., although minimal effective concentrations of micafungin and anidulfungin are 2- to 10-fold lower than those for caspofungin. Synergistic/additive in vitro effects of echinocandins when combined with a polyene or azole have been observed. Clinical resistance to the echinocandins is rare despite case reports of caspofungin resistance in several Candida spp. Resistance has been attributed to mutations in the FKS1 gene within two hot spot regions, leading to amino acid substitutions, mostly at position 645 (serine), yet not all FKS1 mutants have caspofungin MICs of >2?μg/mL. Of the three echinocandins, the in vitro 'paradoxical effect' (increased growth at supra-MIC drug concentrations) is observed least often with anidulafungin. All echinocandins have low oral bioavailability, and distribute well into tissues, but poorly into the CNS and eye. Anidulafungin is unique in that it undergoes elimination by chemical degradation in bile rather than via hepatic metabolism, has a lower maximum concentration and smaller steady state under the concentration-time curve but longer half-life than caspofungin or micafungin. In children, dosing should be based on body surface area. Daily doses of caspofungin (but not micafungin and anidulafungin) should be decreased (from 50 to 35?mg) in moderate liver insufficiency. All echinocandins display concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus) activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5 hours against Aspergillus. The echinocandins are well tolerated with few serious drug-drug interactions since they are not appreciable substrates, inhibitors or inducers of the cytochrome P450 or P-glycoprotein systems. In parallel with the greater clinical experience with caspofungin, this agent has a slightly higher potential for adverse effects/drug-drug interactions, with the least potential observed for anidulafungin. Caspofungin (but not micafungin or anidulafungin) dosing should be increased if coadministered with rifampicin and there are modest interactions of caspofungin with calcineurin inhibitors. All three agents are approved for the treatment of oesophageal candidiasis, candidaemia and other select forms of invasive candidiasis. Only micafungin is licensed for antifungal prophylaxis in stem cell transplantation, whereas caspofungin is approved for empirical therapy of febrile neutropenia. Caspofungin has been evaluated in the salvage and primary therapy of invasive aspergillosis. Combination regimens incorporating an echinocandin showing promise in the treatment of aspergillosis. However, echinocandins remain expensive to use.     

Apotransferrin has a second mechanism for anticandidal activity through binding of Candida albicans

It has been reported that transferrin has antibacterial and antifungal activities via iron chelation in the environment surrounding the microbes. In the present study, we investigated whether the binding of transferrin to Candida albicans mediates growth inhibition. By using cultures that contained iron-free (apo)transferrin glycoprotein either in contact with candidal cells or separated from candidal cells by a dialysis membrane, we distinguished the growth inhibition by transferrin–cell interaction from that of simple iron chelation. Maximal growth inhibition always occurred when the apotransferrin interacted directly with the cells. Additionally, there was partial inhibition even when candidal cells were in contact with iron-saturated transferrin. Binding studies with ⁵⁹Fe³⁺ radiolabeled-transferrin indicated that the apo-protein can bind to the candidal cell surface. The binding sites were saturable and it was dose dependent. Chemicals (hydrogen peroxide, dithiothreitol, sodium dodecyl sulfate) blocked transferrin binding to C. albicans, and among the three, hydrogen peroxide (HP) was the most effective for the blocking. When HP-treated yeast cells were added to the culture that was pretreated with apotransferrin, candidal cell growth increased by 5-fold as compared to the growth of HP-untreated candidal cells under apotransferrin-regulation (P < 0.05). Combined all data together, it was concluded that transferrin has a second mechanism of anticandidal activity that is mediated by binding to the surface of C. albicans yeast cells.     

不同制法纳米银的抗真菌活性研究

目的 探讨不同制备方法得到的纳米银的体外抗真菌活性。 方法 采用微量液基稀释法测定纳米银对氟康唑不同敏感型白色念珠菌的最低抑菌浓度;棋盘实验测定纳米银与氟康唑的协同抗真菌作用。 结果 不同制备方法得到的纳米银对白色念珠菌的抑制作用不同,对敏感菌与耐药菌的抑制作用无显著差异,与氟康唑合用对白色念珠菌能产生协同作用。 结论 不同制备方法得到的纳米银在体外的抗真菌作用有差异,但与氟康唑合用可产生协同作用。     

Synthesis of potential antitubercular and antimicrobial s-triazine-based scaffolds via Suzuki cross-coupling reaction

Two series of bis(3,5-dimethylpiperidinyl)-1,3,5-triazinyl)-N-(phenyl/benzothiazolyl)-acetamides were synthesized so as to investigate their antimicrobial and antimycobacterial actions. Intermediate 4-(4,6-bis(3,5-dimethylpiperidin-1-yl)-1,3,5-triazin-2-yl)aniline was synthesized by palladium-catalyzed Suzuki cross-coupling reaction to furnish C–C bond formation to s-triazine ring. Pharmacological screening against eight bacteria (S. aureus, B. cereus, E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, and S. flexneri), four fungi (A. niger, A. fumigatus, A. clavatus, and C. albicans), and Mycobacterium tuberculosis H37Rv was examined and the effects of various substituents on biological profiles (MIC, 1.56–50 μg/mL) of final analogues were investigated. Four (8c, 8i, 9d, 9j) of the final analogues displayed antimycobacterial activity (3.12–6.25 μg/mL) equipotent to standard drugs.     

Selected essential oils inhibit key physiological enzymes and possess intracellular and extracellular antimelanogenic properties in vitro

Essential oils (EOs) extracted from six medicinal herbs and food plants [Cinnamomum zeylanicum (CZ), Psiadia arguta (PA), Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), and Citrus reticulata (CR)] were studied for any inhibitory potential against key physiological enzymes involved in diabetes (α-glucosidase), skin aging (collagenase and elastase), and neurodegenerative disorders (acetylcholinesterase). Kinetic studies of the active EOs on the aforementioned enzymes were determined using Lineweaver–Burk plots. The intracellular and extracellular antimelanogenic potential of the EOs were evaluated on B16F10 mouse melanocytes. CH and CR were found to significantly inhibit (2.476 ± 0.13 μg/mL and 3.636 ± 0.10 μg/mL, respectively) acetylcholinesterase, compared with galantamine (3.989 ± 0.16 μg/mL). CH inhibited collagenase (50% inhibitory concentration 28.71 ± 0.16 μg/mL) compared with the control (24.45 ± 0.19 μg/mL). The percentage inhibition in the elastase assay of CH was 63.21% compared to the positive control (75.09%). In addition, CH, CR, CGp, CZ, and PT were found to significantly inhibit α-glucosidase (276.70 ± 0.73 μg/mL, 169.90 ± 0.58 μg/mL, 240.60 ± 6.50 μg/mL, 64.52 ± 0.69 μg/mL, and 313.0 ± 5.0 μg/mL, respectively), compared to acarbose (448.80 ± 0.81 μg/mL). Active EOs showed both uncompetitive and competitive types of inhibition. The EOs also inhibited intracellular (50% inhibitory concentration 15.92 ± 1.06 μg/mL, 23.75 ± 4.47 μg/mL, and 28.99 ± 5.70 μg/mL for CH, CR, and CGp, respectively) and extracellular (< 15.625 μg/mL for CH, CR, CGp, and PT) melanin production when tested against B16F10 mouse melanocytes. Results from the present study tend to show that EOs extracted from these medicinal plants can inhibit key enzymes and may be potential candidates for cosmetic and pharmaceutical industries.     

Glutathione sulfotransferase inhibition activity of a self-fermented beverage,Kanji

Context: Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content.

Objectives: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats.

Materials and methods: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001–100.00?mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats.

Results: The GST inhibition activity of Kanji (100.00?μg/mL), methanol extract of D. carota roots (100.00?μg/mL) and tannic acid (10.00?μg/mL, positive control) was found to be 0.162?±?0.016, 0.106?±?0.013 and 0.073?±?0.004?μM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222–0.316?mg/g) and 0.77?mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji.

Discussion: Kanji having solid contents 80.0?μg/mL, equivalent to 0.0025?μg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528?mg/kg, 16.67?μg ferulic acid), to rats indicated poor absorption of ferulic acid.

Conclusion: Kanji having solid contents 14–36?mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.