三萜嗪类化合物，一类对白血病细胞 CCRF-CEM 具有选择性细胞毒性的新型化合物。

Triterpenic azines, a new class of compounds with selective cytotoxicity to leukemia cells CCRF-CEM.

机构信息

Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc, 17 listopadu 1192/12, 771 46 Olomouc, Czech Republic.

Institute of Molecular & Translational Medicine, Faculty of Medicine & Dentistry, Palacky University in Olomouc, Hnevotinska 5, 779 00 Olomouc, Czech Republic.

出版信息

Future Med Chem. 2018 Mar 1;10(5):483-491. doi: 10.4155/fmc-2017-0171. Epub 2018 Feb 9.

DOI:10.4155/fmc-2017-0171

PMID:29424548

Abstract

AIM

From betulinic acid (1a), we synthesized 30-oxobetulinic acid (2a) that is highly cytotoxic against many cancer cell lines; however, its generic toxicity is the main obstacle in further development as cytostatic. Methodology & results: From 2a, we prepared a new class of compounds - nonsymmetrical azines and tested their in vitro cytotoxicity. All new azines with a free 28-COOH group (4a-4e) were highly and selectively cytotoxic against the T-lymphoblastic leukemia cell line CCRF-CEM and exhibited dose-dependent inhibition of RNA and DNA synthesis and other cell-cycle alterations, including the M-phase block.

CONCLUSION

The potential use of azines (4a-4e) in drug development focused on hematological cancers is significantly higher than that of previously studied acids 1a and 2a.

摘要

目的

从白桦脂酸（1a）合成了高度细胞毒性的 30-氧代白桦脂酸（2a），对许多癌细胞系具有细胞毒性;然而，作为细胞抑制剂，其普遍的毒性是进一步开发的主要障碍。

方法与结果

从 2a 我们制备了一类新的化合物 - 不对称嗪类化合物，并测试了它们的体外细胞毒性。所有具有游离 28-COOH 基团的新型嗪类化合物（4a-4e）对 T 淋巴细胞白血病细胞系 CCRF-CEM 具有高度和选择性的细胞毒性，并表现出剂量依赖性地抑制 RNA 和 DNA 合成以及其他细胞周期改变，包括 M 期阻滞。