Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
Planta Med. 2011 May;77(7):711-7. doi: 10.1055/s-0030-1250523. Epub 2010 Nov 5.
The in vitro anticancer activity of eight natural cytochalasins and three hemisynthetic derivatives of cytochalasin B on six cancer cell lines was evaluated. The IC (50) in vitro growth inhibitory concentrations, as determined by an MTT colorimetric assay, ranged between 3 and 90 µM and did not relate to the intrinsic sensitivity of the cancer cell lines to proapoptotic stimuli. Structure activity relationship (SAR) analyses revealed that the presence of an unmodified hydroxyl group at C-7 of the perhydroisoinsolyl-1-one residue as well as the functionalities and the conformational freedom of the macrocycle are all important features for cytochalasin-mediated anticancer activities in vitro. Computer-assisted phase-contrast microscopy revealed two groups of cytochalasins, i.e., cytotoxic versus cytostatic ones. Our data open new possibilities for tuning cytochalasin targets and developing nontoxic, cytostatic cytochalasins to combat cancers associated with poor prognoses, such as those that display intrinsic resistance to proapoptotic stimuli.
评估了八种天然细胞松弛素和三种细胞松弛素 B 的半合成衍生物对六种癌细胞系的体外抗癌活性。通过 MTT 比色法测定的体外生长抑制浓度（IC50）范围在 3 到 90 μM 之间，与癌细胞系对促凋亡刺激的固有敏感性无关。结构活性关系（SAR）分析表明，在全氢异吲哚-1-酮残基的 C-7 位上存在未修饰的羟基以及大环的官能团和构象自由度，都是细胞松弛素介导的体外抗癌活性的重要特征。计算机辅助相差显微镜显示了两组细胞松弛素，即细胞毒性与细胞静止性。我们的数据为调节细胞松弛素靶标和开发非毒性、细胞静止性细胞松弛素以对抗与预后不良相关的癌症（例如对促凋亡刺激具有内在抗性的癌症）开辟了新的可能性。
