کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10584787 981353 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents
ترجمه فارسی عنوان
طراحی، سنتز و ارزیابی میناهای جدید کینازولین-2،4-دیئین به عنوان مهار کننده های سیتانات کیتین و عوامل ضد قارچی
کلمات کلیدی
کوینازولین-2،4-دیون، مهار کننده سنتاز چیتین، سنتاز چیتین، فعالیت ضد قارچی،
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی
A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 5l, and 5o had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08 mmol/L, while polyoxin B as positive drug had IC50 of 0.18 mmol/L. These IC50 values of compounds 5i, 5m, 5n, and 5s were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 5l and 5o were16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c, 5d, 5e and 5l were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 13, 1 July 2014, Pages 3405-3413
نویسندگان
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