与4-乙酰氧基-双去甲基他莫昔芬、雌二醇和二氢睾酮相连的1-(2-氯乙基)-1-亚硝基-3-(2-羟乙基)脲的体外评估
In vitro evaluation of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea linked to 4-acetoxy-bisdesmethyltamoxifen, estradiol and dihydrotestosterone.
作者信息
Kaleagasioglu F, Berger M R, Schmähl D, Eisenbrand G
机构信息
Deutsches Krebsforschungszentrum, Institut für Toxikologie und Chemotherapie, Heidelberg, Fed. Rep. of Germany.
出版信息
Arzneimittelforschung. 1990 May;40(5):603-6.
The anticancer efficacies of three 1-(2-chloroethyl)-1-nitroso-3-(2- hydroxyethyl)urea (HECNU) derivatives--4-acetoxybisdesmethyltamoxifen-1,4-hemisuccinate-H ECNU (4-OAc-BDMT-hs-HECNU), 17-beta-estradiol-1,4-hemisuccinate-HECNU (E2-hs-HECNU) and 17-dihydrotestosterone-1,4-hemisuccinate-HECNU (DHT-hs-HECNU)--are compared with their unlinked equimolar mixtures using the estrogen and androgen receptor positive cell line MCF-7. Following 72 h incubation at a concentration of 100 mumol/l, 4-OAc-BDMT-hs-HECNU and DHT-hs-HECNU have a growth inhibitory effect of 76% and 73%, respectively, whereas E2-hs-HECNU causes an inhibition of 55%. Within this time period, DHT-hs-HECNU (100 mumol/l) is more effective as compared to the unlinked equimolar combination of HECNU plus dihydrotestosterone; E2-hs-HECNU (100 mumol/l) is slightly more and 4-OAc-BDMT-hs-HECNU (100 mumol/l) is even less effective than the respective unlinked equimolar mixtures. At this concentration (100 mumol/l) the growth inhibitory effect of 4-OAc-BDMT-hs-HECNU is not antagonized by coincubation with estradiol.
使用雌激素和雄激素受体阳性细胞系MCF-7，比较了三种1-(2-氯乙基)-1-亚硝基-3-(2-羟乙基)脲（HECNU）衍生物——4-乙酰氧基双去甲基他莫昔芬-1,4-半琥珀酸酯-HECNU（4-OAc-BDMT-hs-HECNU）、17-β-雌二醇-1,4-半琥珀酸酯-HECNU（E2-hs-HECNU）和17-二氢睾酮-1,4-半琥珀酸酯-HECNU（DHT-hs-HECNU）与其未连接的等摩尔混合物的抗癌效果。在100μmol/L浓度下孵育72小时后，4-OAc-BDMT-hs-HECNU和DHT-hs-HECNU的生长抑制作用分别为76%和73%，而E2-hs-HECNU引起的抑制率为55%。在此时间段内，与HECNU加二氢睾酮的未连接等摩尔组合相比，DHT-hs-HECNU（100μmol/L）更有效；E2-hs-HECNU（100μmol/L）略更有效，而4-OAc-BDMT-hs-HECNU（100μmol/L）比各自未连接的等摩尔混合物效果更差。在此浓度（100μmol/L）下，4-OAc-BDMT-hs-HECNU的生长抑制作用不会因与雌二醇共同孵育而受到拮抗。
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