کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1395404 1501123 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds
چکیده انگلیسی


• A novel series of triazole derivatives (3a-h) was designed and synthesised as anticandidal agents.
• The compound 3e showed most potent anticandidal activity with <5% hemolysis and no cytotoxicity against VIRO cell line.
• Synergistic anticandidal activity of 3e in combination with FLC was checked and FICI was calculated.
• QSAR studies were also done for all the derivatives.

In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, 1H, 13C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 93, 26 March 2015, Pages 246–254
نویسندگان
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