7-O-(4-O-乙酰基-3-碘-2,3,6-三脱氧-α-L-阿拉伯己吡喃糖基)柔红霉素酮和7-O-(3-氯-2,3,6-三脱氧-4-O-丙酰基-α-L-来苏己吡喃糖基)柔红霉素酮的设计、合成及生物活性

Design, synthesis and biological activity of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo- hexopyranosyl)daunomycinone.

作者信息

Aligiannis N, Pouli N, Marakos P, Mitaku S, Skaltsounis A L, Leonce S, Pierre A, Atassi G

机构信息

University of Athens, Department of Pharmacy, Panepistimiopolis-Zografou, Greece.

出版信息

Chem Pharm Bull (Tokyo). 2000 Jan;48(1):150-3. doi: 10.1248/cpb.48.150.

DOI:10.1248/cpb.48.150

PMID:10705494

Abstract

The synthesis and pharmacological evaluation of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo-hexopyrano syl) daunomycinone are described. Their cytotoxic activity was evaluated against normal and resistant cell lines. Both compounds exhibited activity against the adriamycin resistant cell line KB-A1. These results support the hypothesis that the increased lipophilicity of the sugar part of anthracyclines is associated with their ability to overcome multidrug resistance (MDR).

摘要

描述了7 - O -（4 - O - 乙酰基 - 3 - 碘 - 2,3,6 - 三脱氧 - α - L - 阿拉伯 - 己吡喃糖基）柔红霉素酮和7 - O -（3 - 氯 - 2,3,6 - 三脱氧 - 4 - O - 丙酰基 - α - L - 来苏 - 己吡喃糖基）柔红霉素酮的合成及药理评价。评估了它们对正常细胞系和耐药细胞系的细胞毒性活性。这两种化合物均对阿霉素耐药细胞系KB - A1表现出活性。这些结果支持了如下假说：蒽环类药物糖部分亲脂性的增加与其克服多药耐药性（MDR）的能力相关。