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

作者：Wang, Zhiwei; Qi, Huan; Shen, Qirong; Lu, Guodong; Li, Mingyang; Bao, Kai; Wu, Yingliang^*; Zhang, Weige^*

来源：European Journal of Medicinal Chemistry, 2016, 122: 520-529.

DOI：10.1016/j.ejmech.2016.06.055

• Combretastatin A-4/oltipraz hybrids
• Antiproliferative activity
• Tubulin polymerization
• Cell cycle arrest
• Molecular modelling studies

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 mu M 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.

• 出版日期2016-10-21
• 单位锦州医科大学; 沈阳药科大学