• Archives of Pharmacal Research
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• v.20 no.6
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• pp.586-589
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• 1997

Antifungal activities of 6-[(N-4-bromophenyl)amino]-7-chloro-5,8-quinolinedione (RCK7) were tested. The MIC values of RCK7 were determined for antifungal suceptibility, in vitro against Aspergillus niger, Cryptococcus neoformans and Trichophyton mentagrophyte by standard agar streak method. In vitro, RCK7 showed more potent antifungal activity than fluconazole and ketoconazole. Also, RCK7 was tested for in vivo antifungal activity in the treatment of systemic infection with Candida albicans in normal mice. The therapeutic potential of RCK7 had been assessed by evaluating their survival rate against systemic infections compared with that of ketoconazole. $ED_{50}$ of intraperitoneally administered RCK7 ws $2.05{\pm}0.30mg/kg$ but that of ketoconazole was $8.00{\pm}0.73 mg/kg$, respectively. When RCK7 was administered intravenously at the $ED_{50}$(2.05 mg/kg). the colony counts of Candida albicans in the liver after 7 days and 14 days were reduced as likely as ketoconazole at the $ED_{50}(8.00 mg/kg)$, and the better survival rates than ketoconazole's were achieved after 14 days. The results suggest that RCK7 may be a potent antifungal agent.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.306.1-306.1
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• 2003

The purpose of this study was to investigate the effect of ketoconazole(20mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel(40mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with ketoconazole was increased significantly (coadministration p<0.05, pretreatment p<0.01) compared to that of control. (omitted)

• Bulletin of the Korean Chemical Society
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• v.24 no.4
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• pp.460-466
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• 2003

For the drug master file (DMF) of ketoconazole, four impurities (1-4) contained in ketoconazole were synthesized. During the synthesis of 2, a new synthetic method of 1,4-dihydropyrazine was established. To oxidize the aminoalcohol (2j) to the aminal (2j-1), the standard Swern oxidation condition was modified to mask the nucleophilicity of the amino group temporarily using one equivalent of acetic acid. Derivative 3 was synthesized via regioselective bromination at the 2 position of the 4-aminophenol derivative (3a) using $Br_2$ in the presence of p-TsOH. The etherification of aryl bromide with the phenol derivative (1f) was accomplished by a modification of the general Cu-mediated reaction condition using excess 1f itself as a solvent at elevated temperature (190 ℃).

• Natural Product Sciences
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• v.11 no.2
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• pp.92-96
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• 2005

The antifungal activities of essential oils from the leaves of Glehnia littoralis, which is cultivated in Korea, were evaluated against pathogenic Trichophyton species by the broth dilution method and the disk diffusion test. Additionally, the effects of the oils together with ketoconazole were tested by the checkerboard titer test. The essential oil fraction and its main components showed significant inhibition of the tested Trichophyton fungi, with minimal inhibitor concentrations (MICs) in the range of 16-32 mg/ml. The results suggest that activities of this oil are based mainly on the contents of ${\alpha}-pinene$ (22.17%), the next prominent component of the oil fraction, while the first main components ${\beta}-pinene$ (57.83%) have relatively mild activity. The MICs of ${\alpha}-pinene$ and ${\beta}-pinene$ were 1-4 mg/ml and 4-32 mg/ml, respectively. Additionally the Glehnia oil fraction and its main components as well, exhibited significant synergism with ketoconazole against Trichophyton rubrum.

• YAKHAK HOEJI
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• v.46 no.3
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• pp.203-207
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• 2002

The antifungal activities of the essential oils from Anthemis nobilis, Ciderus atlantica, Juniperus communis, Lavandula angustifolia, Pelargonium graveolens, Pogestemon patchouli, Rosmarinus officinalis, and Styrax tonkinensis which are recommended for the treatment of microbial infections in aromatherapy and complementary medicines were tested against Candida spp. The activities were measured by broth dilution method and disk diffusion assay. Most of the test oils inhibited growth of Candida albicans, C. utilis and C. tropicalis. Especially, the essential oil from Pelargonium graveolens and its main component, citronellol showed the strongest activity among the herbs except benzoic acid from Styrax tonkinensis which is well-known antimicrobial compound. As a result of checkerboard microtiter test. synergistic effect of citronellol, was shown when the component was combinated with ketoconazole, displaying a fractional inhibiting concentration (FIC) index of 0.37 against C. albicans.

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.389-393
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• 2003

The essential oils from Cedrus atlantica, Styrax tonkinensis, Juniperus communis, Lavandula angustifolia, Melaleuca alternifolia, Pelargonium graveolens, Pogestemon patchouli and Rosmarinus officinalis were analyzed by GC-MS. Antifungal activities of the oils were investigated by disk diffusion assay and the broth dilution method against Aspergillus niger and A. flavus. The effects of geraniol and the essential oil fraction from P. graveolens on the antifungal activity of amphotericin Band ketoconazole were examined using a checkerboard microtiter assay against both Aspergillus fungi. Most of the tested essential oils, with the exception of C. atlantica, J. communis, and P. patchouli, significantly inhibited growth of A. niger and to a lesser extent that of A. fIavus, with MICs (minimal inhibitory concentrations) in the range 0.78-12.5 mg/mL. The essential oil fraction of P. graveolens and its main components, geraniol and citronellol, exhibited additive effects with amphotericin B and with ketoconazole against both Aspergillus species, resulting in fractional inhibitory concentration (FIC) indices ranging from 0.52 to 1.00.

• Journal of the Korean Applied Science and Technology
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• v.16 no.4
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• pp.299-306
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• 1999

For the synthesis of new antifungal agents, We have synthesized four new ketoconazole derivatives were synthesized by the reaction of cis-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1,3-dioxolan-4-yl]methane sulfonate with isolated fig compounds. These compounds were showed strong antifungal activity against C, albicans ATCC 10231. C, utilis. S, cerevisiae ATCC 9763. A and niger ATCC 9029. Among them, sample No.(13) showed potent inhibition activity. Generally, other samples showed biological activity in vitro test. The above results showed the possibility of the development of new antifungal agents.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.417-424
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• 2011

Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. KET inhibits C17-20 lyase which blocks the conversion of 17 ${\alpha}$-hydroxyprogesterone to androstenedione. The effect of Cuscutae semen(CS) extract against KET-induced testicular damage was evaluated in male rats. CS extract was administered orally (100 and 200 mg/kg) for 26 days. Three weeks after CS extract administration, KET was CS-administered intraperitoneally at a dose of 100 mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidant enzymes were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of CS extract. This study suggests a protective role of Cuscutae semen extract that could be attributed to its antioxidant properties.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.197-200
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• 1996

6-[(N-2,3-Dichlorophenyl)aminol-7-chloro-5,8-quinolinedione (RCK1 1) was tested for in vivo antifungal activities in the treatment of systemic infection with Canclicla albicans in normal mice compared with ketoconazole. The therapeutic potential of RCK11 had been assessed by evaluating their activities (survival rates) against systemic infections in normal mice. $ED_{50}$ of intraperitoneally administered RCK11 was $0.10\pm0.01 mg/kg$ but that of ketoconazole had $8.00\pm0.73 mg/kg$ respectively. When RCK11 was administered intravenously at the $ED_{50}$(0.10 mg/kg), the colony counts of Canoliola albicans in the liver after 7 days and 14 days were reduced as likely as ketoconazole at the $ED_{50}$ (8.00 mg/kg), and the better survival rates than ketoconazole were achieved after 14 days. The results suggest that RCK11 may be a potent antifungal agent.

• The Journal of the Korean Society for Microbiology
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• v.22 no.4
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• pp.435-443
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• 1987

A total of 30 strains of Candida albicans were examined for susceptibility to amphotericin B and ketoconazole using Sabouraud's dextrose broth, Kimmig broth and Supplemented yeast nitrogen base broth media. Furthermore, the growth curve and colony forming units were checked for use of stationary-phase cells and 2-hour incubation cells in the absence of atifungal agents. The viable counts were determined periodically during incubation by standard plate count techniques. The minimum inhibitory concentrations of amphotericin B for use of stationary phase cells were as follows: SDB, $0.09{\sim}0.97mcg/ml$(0.39mcg/ml); Kimmig broth, $0.19{\sim}0.39mcg/ml$(0.42 mcg/ml) and SYNB, $0.19{\sim}0.39mcg/ml$mcg/ml(0.23mcg/ml). In ketoconazole, MICs were value SDB, $3.12{\sim}25.0mcg/ml$(12.5mcg/ml); Kimmig broth, $12.5{\sim}25.0mcg/ml$ (22.5mcg/ml) and SYNB, $3.12{\sim}12.5mcg/ml$(6.71mcg/ml). The MICs of amphotericin B(0.2mcg/ml cone.) for use of 2-hour incubation cells in absence of AMB were, SDB, $0.04{\sim}0.39mcg/ml$(0.11mcg/ml); Kimmig broth, $0.09{\sim}0.39mcg/ml$(0.18mcg/ml) and SYNB, $0.09{\sim}0.19mcg/ml$(0.14mcg/ml) and in KTZ, the value of MICs were SDB, $3.12{\sim}25.0mcg/ml$(12.22mcg/ml); Kimmig broth, $0.78{\sim}25.0mcg/ml$(11.01mcg/ml) and SYNB, $1.56{\sim}12.5mcg/ml$(3.90mcg/ml). The two-log reductions in CFU per milliliter observed when 2 hour preincubation cells were treated with 0.2mcg/concentrations of AMB and 25.0mcg/ml of KTZ. However, AMB treated cells were restored to growth activity, it suggested that the AMB has no active antifungal activity.