Structure—activity relationship of alkyl 9—nitrocamptothecin esters

编号 zgly0000315131

文献类型 期刊论文

文献题名 Structure—activity relationship of alkyl 9—nitrocamptothecin esters

作者 Zhi-SongCAO  PanayotisPANTAZIS 

作者单位 TheStehlinFoundationforCancerResearchatSt.JosephHospital 

母体文献 Acta Pharmacologica Sinica;中国药理学报: 英文版 

年卷期 2003,24(2)

页码 109-119

年份 2003 

分类号 R284.1 

关键词 喜树碱  脂类  抗肿瘤药物  构效关系 

文摘内容 AIM:To study the structure-activity relationship of alkyl 9-nitrocamptothecin esters .METHODS:Two alkyl 9-nitrocamptothecin(9NC) esters 5g and 5h were prepared by esterification reactions of 9NC with valeric anhydride and heptanoic anhydride,respectively,Eight 9NC esters 5a-5h were tested for cytotoxicity against human leukemia cell lines HL-60 and U-937 Flow cytometry analysis was used to identify the cell cycle phase trageted by the esters and quantify the extent of ester-induced cell death (apoptosis).RESULTS:Esters 5b and 5c demonstrated great abilities to inhibit growth of the leukemia cells followed by induction of apoptosis;esters 5a ,5e,and 5g induced silight perturbations in the cell cycle at high concentrations;and esters 5d ,5f,and 5h were completely inactive against the cell lines tested.Thus these esters showed the cell anti-proliferative activity in and order of 5b≈5c>5a≈5e≈5g>5d≈5f≈5h.Esters 5b,5c,and 5e were tested in vivo against various human carcinomas in nude mice grown as xenografts.Only 5b and 5c showed a significant antitumor activity,Particularly ,ester 5b demonstrated an antiumor activity agalnst a broad spectrum of human carcinomas including breast,lung,colon,pancreas,stomach,ovarian ,and melanoma,etc.CONCLUSION:These esters act like prodrugs of their parental 9-nitrocamptothecin.High doses need to be administered to animals in order to inhibit growth,and induce reression,of human tumor xenografts in nude mice.These compounds may be developed into potent anticancer drugs due to their low toxictiy。