CAJ | 학술논문

目的研究在喜树碱类化合物A环9,10位上增加一个六元环后,所得衍生物的生物活性的变化情况.方法分别以10-羟基喜树碱和7-乙基-10-羟基喜树碱(SN-38)为原料,通过三或四步反应得到一系列相应的A环上修饰的喜树碱衍生物,用MTT法评价了它们的细胞毒活性,用小鼠肝癌H22评价它们体内的肿瘤抑制率.结果 5个六环喜树碱衍生物为目标化合物,10个衍生物为新化合物.结论喜树碱A环的9,10位增加一个"1,4-氧嗪-2-酮"六元环后,其抗肿瘤活性要比喜树碱或10-羟基喜树碱的活性降低.
목적연구재희수감류화합물A배9,10위상증가일개륙원배후,소득연생물적생물활성적변화정황.방법분별이10-간기희수감화7-을기-10-간기희수감(SN-38)위원료,통과삼혹사보반응득도일계렬상응적A배상수식적희수감연생물,용MTT법평개료타문적세포독활성,용소서간암H22평개타문체내적종류억제솔.결과 5개륙배희수감연생물위목표화합물,10개연생물위신화합물.결론희수감A배적9,10위증가일개"1,4-양진-2-동"륙원배후,기항종류활성요비희수감혹10-간기희수감적활성강저.
Aim To improve the biological activity of A-ring modified analogues of camptothecin.Methods A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTT assay,and their in vivo antitumor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds. Conclusion The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of Aring will reduce the antitumor activity of camptothecins.