Antioxidative and antitumor activity of derivatives of 4-beta-amino-4 '-demethylepipodophyllotoxin and their structure-activity relationship

doi:10.1691/ph.2007.6.6667

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	Antioxidative and antitumor activity of derivatives of 4-beta-amino-4 '-demethylepipodophyllotoxin and their structure-activity relationship
	Zhang, XY; Li, WG; Wu, YJ; Tian, X; Zhang, XY (reprint author), Lanzhou Univ, Coll Basic Med Sci, Lanzhou 730000, Peoples R China.
刊名	PHARMAZIE
	2007-06
卷号	62 期号:6 页码:432-438
ISSN号	0031-7144
DOI	10.1691/ph.2007.6.6667
文献子类	Article
英文摘要	The purpose of this study was to investigate antioxidative and antitumor activity of derivatives of 4-beta-amino-4'-demethylepipodophyllotoxin (DmePod) and to analyze their structure-activity relationship. Homogenates of liver, heart and kidney of rats were used to measure malondialdehyde (MDA) generation spontaneously formed or induced by a hydroxyl free radical generation system (Fe2+-ascorbic acid) using thiobarbituric acid (TBA) assay. H2O2-induced red blood cells (RBC) hemolysis was determined spectrophotometrically. Superoxide anion (O2(center dot-)) from zymosan-stimulated neutrophils of rats was evaluated by nitroblue tetrazolium (NBT) reduction assay. Microculture tetrazoliurn (MTT) assay was used to determine the antitumor effects on K562 and K562/DOX cells. The results showed that all the tested compounds strongly inhibited MDA formation from tissue homogenates in a concentrationdependent manner following the rank GP70H > GP7 > VP16 and GP7H > DmePod > Pod. The potency of antihemolysis for DmePod, GP7, GP70H, GP7H and VP16 was similar among them according to their IC50 values by 13.6, 8.6, 11.7, 10.3, and 9.47 mu mol . L-1, respectively, whereas the potency for Pod was the weakest (IC50 > 320 mu mol . L-1). GP7, GP70H and VP16 (160 similar to 320 mu mol . L-1) significantly inhibited O - formation following the potency rank VP16 > GP7 > GP70H. However, 320 mu mol . L-1 of DmePod, Pod or GP7H had no effect on O-2(center dot-) formation. Meanwhile, all the tested compounds strongly inhibited K562 and K562/DOX cell proliferation for 96 h in a concentration-dependent manner. The resistance magnitude of GP7, GP70H, VP16, and DmePod was 2.05, 2.21, 14.29, and 3.26, respectively, while antitumor activity of Pod and GP7H on K562/DOX cells was the weakest in all compounds. Taken together, the introduction of nitroxyl radical moieties into DmePod greatly enhances antioxidative and antitumor activity, and reverses drug resistance. Both NO center dot and NOH groups are essential active moieties.
学科主题	Pharmacology & Pharmacy ; Chemistry
出版地	ESCHBORN
语种	英语
WOS记录号	WOS:000247364600008
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/121367]
专题	基础医学院_期刊论文
通讯作者	Zhang, XY (reprint author), Lanzhou Univ, Coll Basic Med Sci, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Zhang, XY,Li, WG,Wu, YJ,et al. Antioxidative and antitumor activity of derivatives of 4-beta-amino-4 '-demethylepipodophyllotoxin and their structure-activity relationship[J]. PHARMAZIE,2007,62(6):432-438.
APA	Zhang, XY,Li, WG,Wu, YJ,Tian, X,&Zhang, XY .(2007).Antioxidative and antitumor activity of derivatives of 4-beta-amino-4 '-demethylepipodophyllotoxin and their structure-activity relationship.PHARMAZIE,62(6),432-438.
MLA	Zhang, XY,et al."Antioxidative and antitumor activity of derivatives of 4-beta-amino-4 '-demethylepipodophyllotoxin and their structure-activity relationship".PHARMAZIE 62.6(2007):432-438.