具有细胞毒性和抗氧化活性的新型半合成鬼臼毒素类自旋标记衍生物。

Novel semisynthetic spin-labeled derivatives of podophyllotoxin with cytotoxic and antioxidative activity.

机构信息

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.

出版信息

Bioorg Med Chem Lett. 2010 Feb 1;20(3):983-6. doi: 10.1016/j.bmcl.2009.12.048. Epub 2009 Dec 22.

DOI:10.1016/j.bmcl.2009.12.048

PMID:20053564

Abstract

A series of novel spin-labeled podophyllotoxin derivatives were synthesized by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy carbonyl)-amino acids with 4beta-amino-4'-demethylepipodophyllotoxin. The synthesized derivatives 12a-g were evaluated for the partition coefficients, cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI-8226) and antioxidative activities in tissues of SD rats by the TBA method. The vast majority of target compounds have shown superior or comparable activities against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more significant antioxidative activities and superior water solubility than VP-16.

摘要

一系列新型的氮氧自由基标记的鬼臼毒素衍生物通过相应的 N-(1-氧代-2,2,6,6-四甲基-4-哌啶基氧羰基)-氨基酸与 4β-氨基-4′-去甲表鬼臼毒素反应合成。合成的衍生物 12a-g 进行了分配系数的评估，对三种肿瘤细胞系（A-549、HL-60 和 RPMI-8226）的体外细胞毒性和 TBA 法测定的 SD 大鼠组织中的抗氧化活性进行了评价。与 VP-16 相比，绝大多数目标化合物对 A-549、HL-60 和 RPMI-8226 的活性均有提高或相当，且具有更显著的抗氧化活性和更高的水溶性。