کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394940 1501094 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
4,5-Diaryl-3H-1,2-dithiole-3-thiones and related compounds as combretastatin A-4/oltipraz hybrids: Synthesis, molecular modelling and evaluation as antiproliferative agents and inhibitors of tubulin
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
4,5-Diaryl-3H-1,2-dithiole-3-thiones and related compounds as combretastatin A-4/oltipraz hybrids: Synthesis, molecular modelling and evaluation as antiproliferative agents and inhibitors of tubulin
چکیده انگلیسی


• The combretastatin A-4/oltipraz hybrids were first introduced into CA-4 analogues.
• A set of 4,5-diaryl-3H-1,2-dithiole-3-thiones and related compounds were synthesized.
• 4d and 5c showed potent antiproliferative activities at sub-micromolar IC50 values.
• 4d inhibited tubulin polymerization and caused cellular arrest in the G2/M phase.
• 4d was docked with a superimposed docked pose of CA-4.

A new series of 4,5-diaryl-3H-1,2-dithiole-3-thiones and related compounds were designed and synthesised as combretastatin A-4/oltipraz hybrids. We evaluated the antiproliferative activities, inhibition of tubulin polymerization, and cell-cycle effects of these compounds. Several compounds in this series, such as 4d and 5c, displayed significant activity against SGC-7901, KB and HT-1080 cell lines, as determined using MTT assays. The most active compound, 4d, markedly inhibited tubulin polymerization, with an IC50 value of 4.44 μM being observed. In mechanistic studies, 4d caused cell arrest in G2/M phase, induced apoptotic cell death, and disrupted microtubule formation. Molecular docking studies revealed that 4d interacts and binds efficiently with the tubulin protein.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 122, 21 October 2016, Pages 520–529
نویسندگان
, , , , , , , ,