School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Eur J Med Chem. 2013 Jul;65:21-31. doi: 10.1016/j.ejmech.2013.04.031. Epub 2013 Apr 23.
A series of novel N(2)-alkylated quaternary β-carbolines was synthesized by modification of position-1, 2, 7 and 9 of β-carboline nucleus with various alkyl and arylated alkyl substituents, and their cytotoxic activities in vitro and antitumor potencies in mice were evaluated. Compound 3m was found to be the most potent antitumor agent. SARs analysis revealed that (1) the substituents in position-2 and 9 of β-carboline nucleus played a vital role in modulation of antitumor activity; (2) the benzyl and 3-phenylpropyl substituents in position-2 and 9 of β-carboline ring were the optimal substituents giving rise to significant antitumor agent. These compounds might be a novel promising class of antitumor agents with clinical development potential.
一系列新型 N(2)-烷基化的季铵 β-咔啉通过β-咔啉核的 1、2、7 和 9 位的各种烷基和芳基烷基取代基的修饰而合成，并对其体外细胞毒性活性和在小鼠体内的抗肿瘤效力进行了评价。化合物 3m 被发现是最有效的抗肿瘤剂。构效关系分析表明：（1）β-咔啉核的 2 位和 9 位的取代基在调节抗肿瘤活性方面起着至关重要的作用；（2）β-咔啉环的 2 位和 9 位的苄基和 3-苯基丙基取代基是产生显著抗肿瘤剂的最佳取代基。这些化合物可能是一类具有临床开发潜力的新型有前途的抗肿瘤药物。
