ANTINEOPLASTIC ACTIVITY OF DIDEMNIN CONGENERS - NORDIDEMNIN AND MODIFIED CHAIN ANALOGS

被引：35

作者：

JOUIN, P ^{[1
]}

PONCET, J ^{[1
]}

DUFOUR, MN ^{[1
]}

AUMELAS, A ^{[1
]}

PANTALONI, A ^{[1
]}

CROS, S ^{[1
]}

FRANCOIS, G ^{[1
]}

机构：

[1] CNRS,F-31077 TOULOUSE,FRANCE

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 02期

关键词：

D O I：

10.1021/jm00106a002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nordidemnin (2), a natural analogue of the marine cyclodepsipeptide didemnin B (1b), showed cytotoxic activity against L1210 leukemia and antineoplastic activity against P388 leukemia as well as B16 melanoma; nordidemnin (2) was as active as didemnin B (1b). The influence of synthetic modifications in the linear peptidic chain on in vitro and in vivo activity was also studied. Replacement of the terminal lactyl residue by mandelyl and 3-(p-hydroxyphenyl)propionyl residues in compounds 3 and 4, respectively, did not affect the cytotoxic activity against L1210 leukemia (ID50 of 1.1 nM and 1.2 nM, respectively) or the in vivo activity against P388 leukemia. Unlike these aromatic substituants, the lipophilic palmityl residue induced a dramatic loss in cytotoxic activity. The inverted chirality of the MeLeu joining residue in compound 6 caused a marked reduction in the in vitro activity.

引用

页码：486 / 491

页数：6

共 17 条

[1] DIDEMNIN-B - COMPARATIVE-STUDY AND CONFORMATIONAL APPROACH IN SOLUTION [J].