FR209602 and related compounds, novel antifungal lipopeptides from coleophoma crateriformis no. 738. II. In vitro and in vivo antifungal activity

The biological activities of the novel echinocandin-like lipopeptides, FR209602, FR209603 and FR209604, were evaluated. These compounds showed antifungal activity against Candida albicans and Aspergillus fumigatus attributed to inhibition of 1,3-beta-glucan synthesis. The minimum effective concentrations of these compounds against C. albicans and A1. fumigatus ranged from 0.02 to 0.04 microg/ml by microbroth dilution assay, and the IC50 values on C. albicans 1,3-beta-glucan synthase were 0.49, 0.64 and 0.72 microg/ml, respectively. FR209602 and FR209603 showed good efficacy by subcutaneous injection against C. albicans in a murine systemic infection model, with ED50 values of 2.0 and 1.9 mg/kg, respectively.     

Synthesis and antimicrobial activity of some new 2-phenyl-N-substituted carboxamido-1H-benzimidazole derivatives.

Some 1H-benzimidazole-carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated. Compounds 18, 22, and 25 exhibited the best activity against Candida albicans.     

Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis

BACKGROUND: Endogenous tumor necrosis factor-alpha (TNF-alpha) has a beneficial effect as an activation mediator of host defense against infection by the fungus Candida albicans (C. albicans). However, it is unclear whether exogenous TNF-alpha has a beneficial or detrimental effect against Candida. MATERIALS AND METHODS: The direct effect of TNF-alpha on CO2-induced morphological transformation of C. albicans blastoconidia was examined in vitro and the effect of TNF-alpha was determined in a mouse model of oral candidiasis. RESULTS: TNF-alpha suppressed hyphal formation from C. albicans blastoconidia directly and dose-dependently, whereas it did not affect the fungal budding rate at concentrations ranging from 0.01 to 10 microg/ml. In vivo, the oral administration of TNF-alpha significantly reduced the C. albicans CFU in tongue tissues of treated mice. Histopathologically, there was a decrease in the number and size of C. albicans fungi in the tongue tissues. CONCLUSION: Since orally administered TNF-alpha suppressed fungal burden in the tongue tissue without significant detrimental effects, TNF-alpha has potential as a therapeutic agent against Candida.     

Synthesis of some 1-(2,4-dihydroxythiobenzoyl)imidazoles, -imidazolines and -tetrazoles and their potent activity against Candida species

Various 1-(2,4-dihydroxythiobenzoyl)imidazoles, -imidazolines and -tetrazoles were synthesized and evaluated for their in vitro antifungal activity. Compounds were prepared by the reaction of sulfinyl-bis-(2,4-dihydroxythiobenzoyl) with properly substituted azoles. The MIC values against the Candida albicans ATCC 10231 strain, the azole-resistant clinical isolates of C. albicans and non-Candida species were determined. Tetrazole derivatives were the most active against C. albicans, imidazoline derivatives against non-Candida species. All compounds showed higher activity than that of comparable drugs.     

In vitro antifungal activity of N,N-phenyl-1,2,3,4-thiatriazole-5-yl-2,4-beta-resorcylcarbothioamide

The aim of this study was the determination of the antifungal activity of N,N-phenyl-1,2,3,4-thiatriazol-5-yl-2,4-beta-resorcylcarbothioamide (PTR) against Candida albicans, non-albicans Candida species, dermatophytes and moulds and of its influence on the enzymatic activity of C. albicans strains. The reference strains C. albicans ATCC 10231, 200 of C. albicans strains, 7 of non-albicans C. species, 12 dermatophyte strains and 20 mould strains were isolated from different patients. The mean minimum inhibitory concentration (MIC) of PTR against C. albicans strains isolated from patients was 19.6 mg/l, for reference C. albicans ATCC 10,231 it was 12.5 mg/l on Sabouraud's medium (SB). The mean MIC of isolates from patients was 16.9 mg/l, and reference strains 6.25 mg/l on YNB medium, respectively. The MIC of PTR against 7 non-albicans C. species was 27.7 mg/l on SB and 15.6 mg/l on YNB, respectively. The mean MIC of PTR against C. albicans strains isolated from patients was 14.9 mg/l, C. albicans ATCC 10,231 6.25 mg/l and non-Candida species strains 14 mg/l on RPMI medium. The MICs of PTR against dermatophytes ranged from 3 to 25 mg/l. The MICs of PTR against moulds were 25 mg/l and 100 mg/l, respectively. PTR inhibited the enzymatic activity of selected hydrolases of C. albicans and non-Candida species strains. PTR exerts a potent antifungal activity against the yeast-like fungi strains, moulds and dermatophytes. This new compound inhibited the enzymatic activity of selected hydrolases.     

Synthesis and antimicrobial activity of some new 4-hydroxy-2H- 1,4-benzoxazin-3(4H)-ones

Some 4-hydroxy-2H-1,4-benzoxazin-3(4H)-ones were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans. Compounds 9, and 10 exhibited the best activity against Candida albicans.     

Synthesis and antimicrobial activities of some new benzimidazole derivatives

Some benzimidazolylbenzamides were synthesized and their antimicrobial activities against Staphylococcus aureus, Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans evaluated. It was shown that the compound 14 exhibited the best activity against B. subtilis, P. aeruginosa and C. albicans.     

Antibacterial and antifungal compounds. VIII. Synthesis and antifungal activity of pyrrol derivatives similar to trichostatin A

Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.     

Antimicrobial activities of ziziphus abyssinica and berchemia discolor

Aqueous, petroleum-ether, chloroform and dichloromethane extracts of both the barks and leaves of Ziziphus abyssinica and Berchemia discolor were tested for activity against Staphylococcus aureus, Escherichia coli and Candida albicans using the hole plate diffusion and the test tube dilution methods. The aqueous extracts showed significant activity against S. aureus and C. albicans.     

Screening of plants used by North American indians for antifungal,bactericidal, larvicidal and molluscicidal activities

Nineteen plant species from fourteen families used in the traditional medicine of North American Indians have been tested for their fungicidal (Cladosporium cucumerinum, Candida albicans), bactericidal (Bacillus subtilis, Escherichia coli), larvicidal (Aedes aegypti) and molluscicidal (Biomphalaria glabrata) activities. Of the species investigated, 9 were active against Cladosporium cucumerinum, 9 against Candida albicans, 12 against Bacillus subtilis, 18 against Escherichia coli, 3 against Aedes aegypti, and 11 against Biomphalaria glabrata.     

五倍子鞣质提取物对白假丝酵母的抗菌活性研究

目的 研究五倍子鞣质提取物对白假丝酵母的体外抗茵活性.方法 通过超声波提取五倍子有效成分鞣质,福林-酚比色法检测鞣质含量,采用微量稀释法检测五倍子鞣质提取物对白假丝酵母的最低抑菌浓度(MIC)和最低杀菌浓度(MFC),以最低抑茵浓度药物作用白假丝酵母6、12、24h,通过普通光学显微镜直接观察白假丝酵母形态结构的变化,并用吖啶橙/溴化乙锭染色,通过荧光显微镜观察白假丝酵母的死亡方式.结果 五倍子鞣质提取物对白假丝酵母的最低抑菌浓度为10.76 mg/mL,最低杀菌浓度为21.52mg/mL;五倍子鞣质提取物可导致白假丝酵母细胞变形,形态结构改变,最终导致其死亡;同时抑制细胞发芽和假菌丝的形成.结论 五倍子鞣质提取物对白假丝酵母有抑制和杀灭作用.     

Differential effects of the combination of caspofungin and terbinafine against Candida albicans, Candida dubliniensis and Candida kefyr

The activity of caspofungin (CSP) combined with terbinafine (TRB) against Candida dubliniensis, Candida kefyr and azole-resistant Candida albicans was evaluated in vitro by checkerboard analysis. The combination of CSP with TRB resulted in positive interactive effects in vitro against C. albicans and C. kefyr but not against C. dubliniensis. Moreover, true synergism was observed only against TRB resistant strains which became susceptible to this drug in the presence of CSP. In contrast, indifference was observed against strains that were already sensitive to TRB indicating that CSP may inhibit resistance to TRB.     

New beauvericins, potentiators of antifungal miconazole activity, Produced by Beauveria sp. FKI-1366. I. Taxonomy, fermentation, isolation and biological properties

Three new beauvericins, designated beauvericins D, E and F, were isolated along with known beauvericin and beauvericin A, from the culture of Beauveria sp. FKI-1366 by solvent extraction, ODS column chromatography and HPLC. These compounds potentiate miconazole activity against not only wild Candida albicans but also fluconazole resistant C. albicans. Beauvericins D and E decreased the IC50 value of miconazole against fluconazole resistant C. albicans from 1.3 microM to 0.25 and 0.31 microM, respectively.     

Possible role of azole and echinocandin lock solutions in the control of Candida biofilms associated with silicone

Until now, management of candidiasis related to implanted devices has remained problematic. The aim of this study was to investigate antifungal lock strategies against Candida albicans and Candida glabrata biofilms in vitro. Three antifungal agents were used against eight C. albicans and six C. glabrata clinical strains isolated from infected catheters. Caspofungin and micafungin, both echinocandins, as well as the azole posaconazole were tested. An in vitro model of Candida biofilm on 100% silicone catheters was used. Efficacy of the antifungal lock was tested against biofilms aged 12h and 5 days following exposure to caspofungin (5mg/L and 25mg/L), micafungin (5mg/L and 15 mg/L) and posaconazole (10mg/L) for 12h. Persistence of antibiofilm activity was investigated 1-3 days following drug elimination. Antifungal lock was considered effective in the event of a significant decrease (P<0.001) in the metabolic activity of the biofilm yeast. The results showed that micafungin had significant inhibitory effectiveness against young and mature C. albicans and C. glabrata biofilms. Moreover, this activity appeared to persist for up to 3 days. Caspofungin displayed similar activity against all C. albicans biofilms, but the activity was less persistent for C. glabrata biofilms. Posaconazole was less effective against C. albicans biofilms, but its activity was sustained. Echinocandin lock therapy could significantly enhance the management of candidiasis in patients with indwelling catheters by combating biofilms and enabling device maintenance in situ.     

Screening of Indonesian Plants for Antifungal and Free Radical Scavenging Activities

A total of 204 crude extracts of Indonesian plants (77 species from 43 families) have been screened for their fungicidal (Cladosporium cucumerinum, Candida albicans) and free radical scavenging [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical] activities. Of the species investigated, 20 were active against Cladosporium cucumerinum, nine against Candida albicans and 24 exhibited radical scavenging properties.     

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. II. In vitro and in vivo activities

FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.     

In vitro synergism between nyasol, an active compound isolated from Anemarrhena asphodeloides, and azole agents against Candida albicans

The antifungal activity of nyasol (NYS) alone or with various antifungal agents was measured in vitro against Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. NYS is a compound recently purified from a medicinal plant, Anemarrhena asphodeloides. Among 12 agents, miconazole (MCZ), ketoconazole (KCZ), clotrimazole (CTZ), and cerulenin showed marked synergistic effects against C. albicans. The fractional inhibition concentration (FIC) indices against 4 strains of C. albicans were 0.067-0.31 for MCZ plus NYS, 0.078-0.31 for KCZ plus NYS, and 0.098-0.13 for CTZ plus NYS. These values indicate the possibility of using NYS as an adjuvant to azole agents in the chemotherapy of candidiasis.     

氮酮对皮肤癣菌和白色念珠菌的体外抑制作用研究

目的 :研究氮酮抗皮肤癣菌和白色念珠菌的作用。方法 :采用美国国家临床标准委员会公布的M27、M38方案和MTT染色法测定氮酮的最低抑菌浓度 (MIC)和最低杀菌浓度 (MFC)。结果 :氮酮对常见真菌的MIC为0 02 % ,对皮肤癣菌的MFC为0 08 %。结论 :氮酮对白色念珠菌有较好的抑菌活性 ,对皮肤癣菌有杀菌活性。     

Synthesis and microbiological activity of some N-(2-hydroxy-4-substitutedphenyl)benzamides,phenylacetamides and furamides as the possible metabolites of antimicrobial active benzoxazoles

The synthesis of some N-(2-hydroxy-4-substitutedphenyl)benzamides, phenylacetamides and furamides as the possible metabolites of benzoxazoles (II1-15) was performed in order to determine their in vitro antimicrobial activity against three Gram-positive bacteria, two Gram-negative bacteria and the fungus Candida albicans and their activities were compared with several control drugs. The compounds II11, II12, and II13 were found active at a MIC value of 12.5 microg/ml against the Gram-negative microorganism Pseudomonas aeruginosa. Most of the compounds show antibacterial activity at MIC a value of 25 microg/ml against the Gram-positive bacteria Staphylococcus aureus. For the antifungal activity against C. albicans, compound II10 was found more active than the other derivatives. The antimicrobial activity of some of these benzamides, phenylacetamides (II1 and II10) which are the possible metabolites of benzoxazoles, was also compared to their corresponding cyclic analogues III-IV. Compound II10 possesses two dilutions better antifungal activity than its cyclic analogue, benzoxazole IV, against C. albicans.     

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. I. Taxonomy of producing strain, fermentation, isolation and biological activities

Two novel antifungal antibiotics, PF1163A and B, were isolated from the fermentation broth of Penicillium sp. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies. PF1163A and B showed potent growth inhibitory activity against pathogenic fungal strain Candida albicans but did not show cytotoxic activity against mammalian cells. These compounds inhibited the ergosterol biosynthesis in Candida albicans.