9-酰氧基玫瑰树碱的合成及其抗肿瘤活性

Synthesis and antitumor activity of 9-acyloxyellipticines.

作者信息

Harada N, Ozaki K, Oda K, Nakanishi N, Ohashi M, Hashiyama T, Tsujihara K

机构信息

Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1997 Jul;45(7):1156-62. doi: 10.1248/cpb.45.1156.

DOI:10.1248/cpb.45.1156

PMID:9246749

Abstract

Various kinds of water-soluble 9-acyloxyellipticine derivatives were synthesized in a search for compounds with potent antitumor activity. Antitumor activities against several tumors in mice (P388 leukemia, colon 26, Lewis lung carcinoma and B16 melanoma) were evaluated by using intravenous administration. Many compounds exhibited good antitumor activities; in particular, the glutarate derivative (5o) showed potent antitumor activity. This compound (5o) may be converted to 9-hydroxyellipticine (2) by enzyme-catalyzed hydrolysis in the body.

摘要

为了寻找具有强抗肿瘤活性的化合物，合成了各种水溶性9-酰氧基玫瑰树碱衍生物。通过静脉给药评估了对小鼠几种肿瘤（P388白血病、结肠26、Lewis肺癌和B16黑色素瘤）的抗肿瘤活性。许多化合物表现出良好的抗肿瘤活性；特别是戊二酸酯衍生物（5o）显示出强抗肿瘤活性。该化合物（5o）在体内可能通过酶催化水解转化为9-羟基玫瑰树碱（2）。