• 대한화학회지
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• 제55권2호
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• pp.256-261
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• 2011

Bis acetylated hybrid pyrazoles 을 합성하여 이들 화합물에 대해 녹는점, 원소분석, MS, FT-IR, one-dimensional $^1H,-$ 및 $^{13}C$-NMR로 분석하였다. 합성한 화합물들에 대해 in vitro 항균활성을 Candida sp. namely Candida albicans, Candida glabrata, Candida parapsilosis, Candida dubliniensis 및 Candida tropicali 균에 대해 수행하였다. Pyrazoles의 페닐고리에 작용기($-CH_3$, $-OCH_3$, -F, -Cl, 및 Br)가 있는 화합물은 Candida species에 대해서 강한 활성을 나타내었다.

• 약학회지
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• 제49권4호
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• pp.323-329
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• 2005

Antimicrobial peptides are evolutionary ancient weapons for animal and plant species to depend themselves against infectious microbes. In the present study, we investigated if an antimicrobial peptide was produced from Coptidis Rhizoma. For the determination, protein substance from the medicinal plant was isolated by various preparations. Among the preparations, the protein portion dissolved in phosphate-buffered saline solution (CRP-DS) that contained the most amount of protein $(90\%)$ resulted in maximal inhibition of Candida albicans which causes local and systemic infections. Analyses by gel-electrophoresis and gel-permeation chromatography showed the CRP-DS formed a single band of approximately 11.8 KDa as molecular size. Antifungal activity of the CRP-DS was almost equivalent to antifungal activity by fluconazole, resulting in MIC (minimal inhibitory concentration) of approximately $50{\mu}g/ml$. The antifungal activity was a dose-dependent. The antifungal activity appeared to be inactivated by heat-treatment and ionic strength, respectively. In a murine model, the CRP-DS enhanced resistance of mice against disseminated candidiasis. The HPLC analysis demonstrated maximum $4\%$ of berberine as residual content in the CRP-DS preparation resulted in no influence on the antifungal activity. In addition, protein portion isolated from Phellodendri Cortex producing the alkaloid component like Coptidis Rhizoma had no such anticandidal effect. These results indicate that the protein substance from Coptidis Rhizoma was responsible for the antifungal activity.

• Journal of Microbiology and Biotechnology
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• 제24권7호
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• pp.905-913
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• 2014

Lj-RGD3, an RGD (Arg-Gly-Asp) toxin protein from the salivary gland of Lampetra japonica, exhibits antifungal activity against Candida albicans. Lj-RGD3 has three RGD motifs and shows homology to histidine-rich glycoprotein. We synthesised two mutant derivatives of Lj-RGD3: Lj-26, which lacks all three RGD motifs and contains no His residues; and Lj-112, which lacks only the three RGD motifs. We investigated the effects of the wild-type and mutated toxins on a gram-positive bacterium (Escherichia coli), a gram-negative bacterium (Staphylococcus aureus), and a fungus (C. albicans). rLj-RGD3 and its mutants exhibited antifungal but not antibacterial activity, as measured by a radial diffusion assay. The C. albicans inhibition zone induced by rLj-112 was larger than that induced by the other proteins, and its inhibitory effect on C. albicans was dose-dependent. In viable-count assays, the rLj-112 MIC was $7.7{\mu}M$, whereas the MIC of the positive control (ketoconazole) was $15{\mu}M$. Time-kill kinetics demonstrated that rLj-112 effectively killed C. albicans at $1{\times}$ and $2{\times}$ MIC within 12 and 6 h, respectively. Electron microscopy analysis showed that rLj-RGD3 and rLj-112 induced C. albicans lysis. Our results demonstrate a novel anticandidal activity for rLj-RGD3 and its mutant derivatives.

• 동의생리병리학회지
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• 제26권1호
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• pp.74-80
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• 2012

Candida albicans is a common opportunistic pathogen and is frequently associated with biofilm formation occurring on the surfaces of host tissues and medical devices. On account of the distinct resistance of C. albicans biofilms to the conventional antifungal agents, new strategies are required to cope with these infections. The root of Polygonum cuspidatum has been used for medicinal purposes in East Asia. The aim of this study was to assess the anticandidal potential of the P. cuspidatum ethanol extract by evaluating biofilm formation, integrity of the cell membranes of C. albicans and adhesion of C. albicans cells to polystyrene surfaces. The growth and development of the biofilm was assessed using an XTT reduction assay, and the extract (0.39 mg/ml) significantly reduced ($41.1{\pm}17.8%$) biofilm formation of 11 C. albicans strains. The extract damaged the cell membranes of C. albicans and remarkably inhibited cell adhesion to polystyrene surfaces. The plant extract displayed fungistatic activity without significant hemolytic activity. Based on the results of this study, the P. cuspidatum extract has promising potential for use in treating biofilm-associated Candida infection.

• Molecules and Cells
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• 제28권4호
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• pp.403-406
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• 2009

Rev is an essential regulatory protein for HIV-1 replication. Rev (11-20) is known as the significant region regarding the function of a nuclear entry inhibitory signal (NIS) of Rev. In this study, anticandidal effects and mechanism of action of Rev (11-20) were investigated. The result exhibited that Rev (11-20) contained candidacidal activities. To understand target site(s) of Rev (11-20), the intracellular localization of the peptide was investigated. The result showed that Rev (11-20) rapidly accumulated in the fungal cell surface. The cell wall regeneration test also indicated that Rev (11-20) exerted its anticandidal activity to fungal plasma membrane rather than cell wall. The fluorescent study using 1,6-diphenyl-1,3,5-hexatriene (DPH) further confirmed the membrane-disruption mechanism(s) of Rev (11-20). The present study suggests that Rev (11-20) possesses significant potential regarding therapeutic agents for treating fungal diseases caused by Candida species in humans.

• 약학회지
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• 제55권3호
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• pp.234-239
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• 2011

Glycycoumarin, a 3-arylcoumarine isolated from Glycyrrhizae radix (a family of Leguminosae), is reported to have anti-bacterial activity. However, its antifungal activity is still unknown. In this present study, the antifungal activity of glycycoumarin (GLM) against Candida albicans, a polymorphic fungus was investigated. Possible mechanism such as blocking of the hyphal induction was also analyzed. By the in-vitro susceptibility analysis, GLM showed anticandidal activity, resulting in an almost complete inhibition of the fungal growth at a concentration of 320 ${\mu}g/ml$, which was equivalent to the efficacy of fluconazole at the same dose. In the murine model of disseminated candidiasis GLM enhanced resistance of mice against the disseminated disease (P<0.05), resulting in 60% protection of GLM-treated mice group during a period of 21-day observation. As for its mechanism of the antifungal activity, GLM blocked hyphal production, one of the important of virulence factors by the fungus, from the yeast form of C. albicans (P<0.01). These data indicate that GLM may contribute to the perspectives that focus on the development of a novel agent with antifungal activity specific for C. albicans infection.

• Journal of Microbiology and Biotechnology
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• 제17권8호
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• pp.1324-1329
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• 2007

Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring, multi-biofunctional chemical existing in grapes and various other plants as a polyphenol type, and it is one of the best known natural anticancer and antiatherosclerosis reagents. In this study, we investigated the antifungal action by resveratrol in Candida albicans, which is a human infectious fungi as an agent of candidiasis. Resveratrol displayed potent fungicidal activity in an energy-dependent manner, without any hemolytic effects against human erythrocytes. It was found that the serum-induced mycelial forms, which playa crucial role in the pathogenesis of C. albicans during host tissue invasion, were disrupted by resveratrol. To understand the correlation between lethal effects and resveratrol action, we examined the physiological changes of C. albicans. A significant accumulation of intracellular trehalose was induced by stress responses to resveratrol action, and a remarkable arrest of cell-cycle processes at the S-phase in C. albicans occured. Therefore, the fungicidal effects of resveratrol demonstrate that this compound is a potential candidate as an antifungal agent in treating infectious diseases by candidal infections.

• Archives of Pharmacal Research
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• 제28권8호
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• pp.963-969
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• 2005

Many reports have stated that some of the pathogenic bacteria can obtain iron from ferroproteins, such as cytochrome C, ferritin, hemin, hemoglobin, and myoglobin. These reports prompted us to determine if an opportunistic pathogenic fungus, Candida albicans, can utilize ferroproteins to circumvent the iron-regulatory effect of transferrin. The following assays were carried out to measure in vitro growth stimulation by the ferroproteins: as an initial step, C. albicans was cultured in iron-free (pretreated with apotransferrin for 24h) culture medium. Once Candida albicans yeast cell growth reached stasis from iron starvation, individual ferroproteins were added to the culture media. Results showed that hemin, hemoglobin, and myoglobin supported a partial growth recovery. Additional studies with haptoglobin, a serum protein that interacts with the globin moiety of certain ferroproteins, established that C. albicans could obtain iron from the haptoglobin-ferroprotein complexes. These data indicate that the heme part of the ferroproteins is the source of iron. This implies that heme oxygenase, CaHMX1 might be involved in bringing about dissociation of heme-containing protein for iron-acquisition. In addition, anticandidal activity of transferrin takes place not only by the process of iron regulation, but also by direct interaction with the yeast cells.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1827-1834
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• 2020

Candida albicans is a major fungal pathogen in humans. In our previous study, we reported that an ethanol extract from Aucklandia lappa weakens C. albicans cell wall by inhibiting synthesis or assembly of both (1,3)-β-D-glucan polymers and chitin. In the current study, we found that the extract is involved in permeabilization of C. albicans cell membranes. While uptake of ethidium bromide (EtBr) was 3.0% in control cells, it increased to 7.4% for 30 min in the presence of the A. lappa ethanol extract at its minimal inhibitory concentration (MIC), 0.78 mg/ml, compared to uptake by heat-killed cells. Besides, leakage of DNA and proteins was observed in A. lappa-treated C. albicans cells. The increased uptake of EtBr and leakage of cellular materials suggest that A. lappa ethanol extract induced functional changes in C. albicans cell membranes. Incorporation of diphenylhexatriene (DPH) into membranes in the A. lappa-treated C. albicans cells at its MIC decreased to 84.8%, after 60 min of incubation, compared with that of the controls, indicate that there was a change in membrane dynamics. Moreover, the anticandidal effect of the A. lappa ethanol extract was enhanced at a growth temperature of 40℃ compared to that at 35℃. The above data suggest that the antifungal activity of the A. lappa ethanol extract against C. albicans is associated with synergistic action of membrane permeabilization due to changes in membrane dynamics and cell wall damage caused by reduced formation of (1,3)-β-D-glucan and chitin.

• 한국미생물·생명공학회지
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• 제41권1호
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• pp.88-95
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• 2013

Candida 바이오필름은 숙주조직과 의료기기의 표면에 자라는 자가-조직화된 미생물의 군락으로 전통적인 항진균제에 대한 저항성이 높게 나타난다. 황금(Scutellaria baicalensis)의 뿌리는 극동지방에서 의료용 목적으로 널리 사용되어 왔다. 본 연구의 목적은 10 C. albicans 임상 분리균주에 의해 형성된 바이오필름에 대한 황금의 수용성 추출물의 효과를 평가하고, 항바이오필름 활성에 대한 메커니즘을 알아보는 것이다. 바이오필름에 대한 효과는 XTT 환원분석법을 사용하였으며, 조사된 모든 균주에 대한 대사활성은 MIC에서 유의하게 감소($57.7{\pm}17.3$%)하였다. 황금추출물은 (1,3)-${\beta}$-D-글루칸 합성효소의 활성을 저해하였고 C. albicans의 형태에 대한 황금의 효과는 글루칸 합성의 억제로 인한 생장의 변화와 관련이 있었다: 대부분의 세포는 둥글고 팽창되었으며 세포벽이 진하게 염색되거나 파열되었다. 항캔디다 활성은 살진균성이었고, 황금은 C. albicans를 $G_0/G_1$기에 머물게 했다. 데이터는 황금이 목표가 되는 균류에 다중의 치명적인 효과를 내며, (1,3)-${\beta}$-D-글루칸 합성효소의 활성을 저해함을 통해 궁극적으로는 세포벽의 파열과 죽음에 이르게 한다는 것을 나타낸다. 따라서 황금은 바이오필름과 관련된 캔디다의 감염을 치료하고 제거하기 위한 항진균제 개발 후보 물질로서의 가능성을 가진다.