QSAR Study of Podophyllotoxin Derivatives as Potential Antitumor Drugs
10.3321/j.issn:1000-467X.2001.04.006
- VernacularTitle:抗肿瘤药鬼臼毒素衍生物构效关系的研究
- Author:
Feng HE
1
;
Yi-Fan LUO
;
Zhi-Yi CHENG
;
Zong-Chao LIU
;
Zhi-Ming LI
;
Bing-Feng XIE
;
Gong-Kan FENG
;
Xiao-Feng ZHU
Author Information
1. Sun Yat-sen University of Medical Sciences
- From:Chinese Journal of Cancer
2001;20(4):368-372
- CountryChina
- Language:Chinese
-
Abstract:
Objective： This study was designed to investigate the three-dimensional quantitative structure-activity relationship (3D-QSAR) and the active sites of podophyllotoxin derivatives. Methods： Twenty-three podophyllotoxin derivatives had been designed to investigate 3D-QSAR against L1210 cells by comparative molecular field analysis (CoMFA), then they were studied by Austin model 1 (AM1) method of quantum chemical calculation. The 3D-QSAR and the active sites were discussed according to their stereo structure and electronic structure. Results： A CoMFA model with considerable predictive ability was established. The results showed that the C4 position was an effective modified point. The steric effect and the electrostatic effect of 4-substituted group were the dominant factor for the activity. The replacement of the “ -NH-” bridge at C4 with the “ -O-” bridge resulted in lowering of the anticancer activity. The results revealed that there was a large electropositive region around the B ring moiety and it could easily combine with an acceptor of the drug. The B ring was essential for the activity. The E ring and its C4′ hydroxyl group also have strong influence on the activity and is an important center of negative electricity within the molecule. Conclusions： The inhibitory activities of the compounds can be predicated by the CoMFA mode. The B ring and E ring are important active sites of the molecule.
