Pharmaceutical Technology Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Arch Pharm Res. 2012 Jan;35(1):35-49. doi: 10.1007/s12272-012-0104-0. Epub 2012 Feb 2.
Two series, a and b, of 3-cyclopentyl or (3-cyclohexyl)-5-substituted-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTT) 2a-9a and 3b, 4b, 6b-9b, were synthesized to develop new cell cycle inhibitors. Variable and promising in vitro antiproliferative activities were shown with the synthesized THTT derivatives. Compound 5a with a 5-cyclopentyl group on position-3 and a glutamine residue on position-5 of the THTT moiety showed maximum activity (IC(50) = 8.98 μM). Compound 5a possessed notable cell cycle disrupting and apoptotic activities with enhanced selectivity against cancer cells, suggesting the potential for the development of new selective cell cycle inhibitors. There is no evident relationship between the cytotoxic activity of the tested compounds and their lipophilicity. In addition, a pharmacophore based study was performed to explain the biological activity on structural bases. A successful model was generated with a good correlation with the observed activity.
两个系列，a 和 b，分别由 3-环戊基或（3-环己基）-5-取代-3,4,5,6-四氢-2H-1,3,5-噻二嗪-2-硫酮（THTT）2a-9a 和 3b、4b、6b-9b 组成，用于开发新的细胞周期抑制剂。合成的 THTT 衍生物表现出可变的、有前途的体外抗增殖活性。具有 5-环戊基取代基和 THTT 部分 5-位上的谷氨酰胺残基的化合物 5a 显示出最大的活性（IC（50）= 8.98 μM）。化合物 5a 具有显著的细胞周期破坏和凋亡活性，并对癌细胞具有增强的选择性，表明有潜力开发新的选择性细胞周期抑制剂。测试化合物的细胞毒性活性与其亲脂性之间没有明显的关系。此外，还进行了基于药效团的研究，以解释结构基础上的生物学活性。生成了一个成功的模型，与观察到的活性具有良好的相关性。
