School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Eur J Med Chem. 2010 Jun;45(6):2503-15. doi: 10.1016/j.ejmech.2010.02.036. Epub 2010 Feb 19.
In a continuing effort to develop novel beta-carbolines endowed with better pharmacological profiles, a series of beta-carboline derivatives were designed and synthesized based on the previously developed SARs. Cytotoxicities in vitro of these compounds against a panel of human tumor cell lines were also investigated. The results demonstrated that the N2-benzylated beta-carbolinium bromides 56-60 represented the most potent compounds with IC50 values lower than 10 microM. The application of 3D-QSAR to these compounds explored the structural basis for their biological activities. CoMFA (q2=0.513, r2=0.862) and CoMSIA (q2=0.503, r2=0.831) models were developed for a set of 47 beta-carbolines. The results indicated that the antitumor pharmacophore of these molecules were marked at position-1, -2, -3, -7 and -9 of beta-carboline ring.
为了开发具有更好药理学特性的新型β-咔啉化合物，我们在之前的 SAR 基础上设计并合成了一系列β-咔啉衍生物。还研究了这些化合物对一系列人肿瘤细胞系的体外细胞毒性。结果表明，N2-苯甲酰基β-咔啉溴化物 56-60 代表了最有效的化合物，其 IC50 值低于 10μM。将 3D-QSAR 应用于这些化合物，探索了它们生物活性的结构基础。建立了一组 47 个β-咔啉的 CoMFA（q2=0.513，r2=0.862）和 CoMSIA（q2=0.503，r2=0.831）模型。结果表明，这些分子的抗肿瘤药效团标记在β-咔啉环的位置-1、-2、-3、-7 和-9。
