D R Phillips, B C Baguley, R T Brownlee, P Cacioli, C J Chandler, I Kyratzis, J A Reiss, P A Scourides
{"title":"双插层双道霉素腙的合成、稳定性和生物活性。","authors":"D R Phillips, B C Baguley, R T Brownlee, P Cacioli, C J Chandler, I Kyratzis, J A Reiss, P A Scourides","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The synthesis of a series of bis-daunomycin hydrazones (5a-g)--all moderately stable at 37 degrees C, pH 6.8, with a half-life of approximately 30 h--is reported. Under a pulse exposure of 2 h they exhibited growth inhibition of mouse L1210 cells, and were 2-3 fold more active than daunomycin. Under continuous exposure growth inhibition conditions with human colon cell lines (HT-29 and HCT-8) they hydrolysed to daunomycin and a partially hydrolysed mono-derivative of daunomycin, and there was no apparent increase in activity over that of the parent anthracycline. Their rate of hydrolysis was observed to increase rapidly with decreasing pH.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"5 3","pages":"203-19"},"PeriodicalIF":0.0000,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The synthesis, stability and biological activity of bis-intercalating bis-daunomycin hydrazones.\",\"authors\":\"D R Phillips, B C Baguley, R T Brownlee, P Cacioli, C J Chandler, I Kyratzis, J A Reiss, P A Scourides\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The synthesis of a series of bis-daunomycin hydrazones (5a-g)--all moderately stable at 37 degrees C, pH 6.8, with a half-life of approximately 30 h--is reported. Under a pulse exposure of 2 h they exhibited growth inhibition of mouse L1210 cells, and were 2-3 fold more active than daunomycin. Under continuous exposure growth inhibition conditions with human colon cell lines (HT-29 and HCT-8) they hydrolysed to daunomycin and a partially hydrolysed mono-derivative of daunomycin, and there was no apparent increase in activity over that of the parent anthracycline. Their rate of hydrolysis was observed to increase rapidly with decreasing pH.</p>\",\"PeriodicalId\":11271,\"journal\":{\"name\":\"Drug design and delivery\",\"volume\":\"5 3\",\"pages\":\"203-19\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1990-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug design and delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug design and delivery","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The synthesis, stability and biological activity of bis-intercalating bis-daunomycin hydrazones.
The synthesis of a series of bis-daunomycin hydrazones (5a-g)--all moderately stable at 37 degrees C, pH 6.8, with a half-life of approximately 30 h--is reported. Under a pulse exposure of 2 h they exhibited growth inhibition of mouse L1210 cells, and were 2-3 fold more active than daunomycin. Under continuous exposure growth inhibition conditions with human colon cell lines (HT-29 and HCT-8) they hydrolysed to daunomycin and a partially hydrolysed mono-derivative of daunomycin, and there was no apparent increase in activity over that of the parent anthracycline. Their rate of hydrolysis was observed to increase rapidly with decreasing pH.