کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1392275 1501127 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structural factors affecting affinity of cytotoxic oxathiole-fused chalcones toward tubulin
ترجمه فارسی عنوان
عوامل ساختاری موثر بر کلکونهای سیتوتوکسیک اکسایتیول به توبولین
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی


• New sub-class of chalcones with high cytotoxic activity.
• Chalcone–tubulin two modes of interaction.
• Relationship between chalcone structure, cytotoxicity and interaction with tubulin.
• Bioequivalence of benzoxathiole and 3,4,5-trimethoxyphenyl units.

Synthesis, in vitro cytotoxic activity, and interaction with tubulin of (E)-1-(6-alkoxybenzo[d][1,3]oxathiol-5-yl)-3-phenylprop-2-en-1-one derivatives (2) are described. Some of the compounds demonstrated cytotoxic activity at submicromolar concentrations, and the activity could be related to interaction with tubulin at the colchicine binding site. Interaction of selected derivatives with tubulin was evaluated using molecular modeling, and two different modes of the interaction were identified. The proposed models demonstrate how particular structural fragments participate in binding to the tubulin and explain the importance of the fragments for cytotoxic activity. It was demonstrated that concerning binding to tubulin, the 6-alkoxybenzoxathiole ring can be considered as structural equivalent of trimethoxyphenyl motif of colchicine, podophyllotoxin or combretastatin A4. The observation opened new ways of rational modifications of several groups of tubulin binders.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 89, 7 January 2015, Pages 733–742
نویسندگان
, , , , , , , , , ,