• 환경생물
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• 제32권1호
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• pp.1-15
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• 2014

양서류는 육상과 수상생태계를 연결하는 먹이사슬의 연결자로 진화적 생태적 지이를 갖는다. 양서류의 배아와 유생은 모체와 독립되어 수환경 내에서 초기발생 및 성장하기 때문에 수환경에 존재하는 다양한 화학물질에 직접적으로 노출될 수 있다. Azole계열 항곰팡이제는 농업 및 의료용으로 널리 사용되는 화학물질로서 농지, 하수처리장 등으로 부터 수계로 유입된다. 최근, 양서류에서 이러한 azole계 물질에 의한 기형유발, 내분비계장애 효과가 증가하고 있다. 본 소고에서는 azole계 물질의 양서류 독성을 파악하고 azole계 물질의 안전한 이용을 위한 가이드라인을 제공하고자 azole계열에 속하는 imidazole, triazole, thiazole, oxazole, pyrazole 항곰팡이 물질이 양서류의 발생, 분화, 생식 등에 미치는 영향에 대해 최근까지의 연구결과를 정리하였다.

• Mycobiology
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• 제45권4호
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• pp.426-429
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• 2017

A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

• Journal of Applied Biological Chemistry
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• 제56권2호
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• pp.109-112
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• 2013

Azole fungicides are one of the most wide-spread antifungal compounds in agriculture and pharmaceutical applications. Their major mode of action is the inhibition of ergosterol biosynthesis, giving depletion of ergosterol, precursors and abnormal steroids. However, metabolic consequences of such inhibition, other than steroidal metabolitesare not well established. Comprehensive metabolic profiles of Saccharomyces cerevisiae has been presented in this study. Wild type yeast was treated either with glucose as control or azole fungicide (ketoconazole). Both polar metabolites and lipids were analyzed with gas chromatography-mass spectrometry. Approximately over 180 metabolites were characterized, among which 18 of them were accumulated or depleted by fungicide treatment. Steroid profile gives the most prominent differences, including the accumulation of lanosterol and the depletion of zymosterol and ergosterol. However, the polar metabolite profile was also highly different in pesticide treatment. The concentration of proline and its precursors, glutamate and ornithine were markedly reduced by ketoconazole. Lysine and glycine level was also decreased while the concentrations of serine and homoserine were increased. The overall metabolic profile indicates that azole fungicide treatment induces the depletion of many polar metabolites, which are important in stress response.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.139-143
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• 2005

Cytochrome P450 14${\alpha}$-sterol demethylase enzyme (CYP51) is the target a of azole type antifungals. The azole blocks the ergosterol synthesis and thereby inhibits fungal growth. A three-dimensional (3D) homology model of CYP51 from Candida albicans was constructed based on the X-ray crystal structure of CYP51 from Mycobacterium tuberculosis. Using this model, the binding modes for the substrate (24-methylene-24, 25-dihydrolanosterol) and the known inhibitors (fluconazole, voriconazole, oxiconazole, miconazole) were predicted from docking. Virtual screening was performed employing Structure Based Focusing (SBF). In this procedure, the pharmacophore models for database search were generated from the protein-ligands interactions each other. The initial structure-based virtual screening selected 15 compounds from a commercial available 3D database of approximately 50,000 molecule library, Being evaluated by a cell-based assay, 5 compounds were further identified as the potent inhibitors of Candida albicans CYP51 (CACYP51) with low minimal inhibitory concentration (MIC) range. BMD-09-01${\sim}$BMD-09-04 MIC range was 0.5 ${\mu}$g/ml and BMD-09-05 was 1 ${\mu}$g/ml. These new inhibitors provide a basis for some non-azole antifungal rational design of new, and more efficacious antifungal agents.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3684-3692
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• 2010

A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to $25\;{\mu}g/mL$, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: $25\;{\mu}g/mL$, $50\;{\mu}g/mL$ and $100\;{\mu}g/mL$ in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

• Mycobiology
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• 제48권2호
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• pp.148-152
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• 2020

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

• 한국임상약학회지
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• 제34권1호
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• pp.71-78
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• 2024

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience. However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA provides some guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted to understand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions: Study finds TKI-DDI not significantly linked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

• Journal of the Korean Wood Science and Technology
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• 제43권1호
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• pp.112-121
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• 2015

국내에서 사용되고 있는 가압주입 처리용 구리 붕소 아졸화합물계의 목재 방부제 Copper Azole (CuAz)의 목재내 주입량별 부후 특성을 조사하였다. 여러 가지 주입량으로 CuAz-2 방부제를 가압주입한 시편을 이용하여 갈색부후균인 부후개떡버섯에 의한 방부효력시험을 실시한 후 질량감소율을 측정하였다. 또한, CuAz-2 처리 시편을 부후개떡 버섯으로 부후시킨 후 광학현미경과 전자현미경으로 부후 특성을 관찰하였다. 그 결과, 부후개떡버섯에 의한 무처리재는 40% 이상의 질량감소율을 보여주었고 실내 부후에 의한 CuAz-2 약제의 방부효력을 나타내는 값은 $1.79{\sim}3.32kg/m^3$이었다. CuAz-2의 주입량에 따라 횡단면, 방사단면, 접선단면에서의 목재조직은 무처리 시편과 비교하여 부후 정도가 다르게 나타났다. 횡단면에서는 조재와 만재부분에서 수직수지구, 방사조직의 부후가 많이 관찰되었고, 방사단면에서는 방사가도관, 방사유세포, 벽공 부분이 부후되어 파괴되었고, 접선단면에서는 방사조직, 수평수지구가 심하게 부후되었다. 따라서 본 연구에서 주입량에 따른 부후 현상이 크게 차이가 난 점 등을 고려하여, 현재의 CuAz-2 주입량에 대한 적정성 검토가 국내 환경에 대해서 이루어져야 할 것으로 생각된다.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3459-3462
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• 2013

• 대한화학회지
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• 제57권6호
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• pp.744-754
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• 2013

Quantitative structure-activity relationship (QSAR) analysis for recently synthesized imidazole-(benz)azole and imidazole - piperazine derivatives was studied for their anticancer activities against breast (MCF-7) cell lines. The statistically significant 2D-QSAR models ($r^2=0.8901$; $q^2=0.8130$; F test = 36.4635; $r^2$ se = 0.1696; $q^2$ se = 0.12212; pred_$r^2=0.4229$; pred_$r^2$ se = 0.4606 and $r^2=0.8763$; $q^2=0.7617$; F test = 31.8737; $r^2$ se = 0.1951; $q^2$ se = 0.2708; pred_$r^2=0.4386$; pred_$r^2$ se = 0.3950) were developed using molecular design suite (VLifeMDS 4.2). The study was performed with 18 compounds (data set) using random selection and manual selection methods used for the division of the data set into training and test set. Multiple linear regression (MLR) methodology with stepwise (SW) forward-backward variable selection method was used for building the QSAR models. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by kNN-MFA, (k-Nearest Neighbor Molecular Field Analysis) investigating the substitutional requirements for the favorable anticancer activity. The results derived may be useful in further designing novel imidazole-(benz)azole and imidazole-piperazine derivatives against breast (MCF-7) cell lines prior to synthesis.