关于一些吡啶并吖啶类海鞘素类似物作为抗肿瘤药物的定量构效关系研究。

QSAR study on some pyridoacridine ascididemin analogues as anti-tumor agents.

作者信息

Debnath Bikash, Gayen Shovanlal, Bhattacharya Subrata, Samanta Soma, Jha Tarun

机构信息

Department of Pharmaceutical Technology, PO Box No. 17020, Jadavpur University, Kolkata -700 032, India.

出版信息

Bioorg Med Chem. 2003 Dec 1;11(24):5493-9. doi: 10.1016/j.bmc.2003.09.022.

DOI:10.1016/j.bmc.2003.09.022

PMID:14642593

Abstract

Pyridoacridine ascididemin analogues have been reported as anticancer agents for their interesting antitumor activity against human cancer cells. A quantitative structure-activity relationship (QSAR) analysis of ascididemin analogues was attempted using the physicochemical parameters and the electrotopological state atom (ETSA) indices. This study indicates that the electron withdrawing substituents with higher MR (molar refractivity) value at R(1) position favor the anti-tumor activity and the presence of NHR (R is hydrogen or alkyl group) at the R(3) position has contribution to the anti-tumor activity. ETSA indices have been incorporated as independent variable in the QSAR model with physicochemical parameters. It clearly suggests the importance of atoms 2, 3, 4, 5, 6 and 7 to the anti-tumor activity.

摘要

吡啶吖啶海鞘胺类似物因其对人类癌细胞具有有趣的抗肿瘤活性而被报道为抗癌剂。尝试使用物理化学参数和电子拓扑状态原子（ETSA）指数对海鞘胺类似物进行定量构效关系（QSAR）分析。该研究表明，在R(1)位置具有较高摩尔折射率（MR）值的吸电子取代基有利于抗肿瘤活性，而在R(3)位置存在NHR（R为氢或烷基）对抗肿瘤活性有贡献。ETSA指数已作为独立变量纳入具有物理化学参数的QSAR模型中。这清楚地表明了原子2、3、4、5、6和7对抗肿瘤活性的重要性。