【摘要】 <正> 近年来,证明了铂化合物具有显著抗癌活性,顺氯氨铂(DDP)已应用于临床,对睾丸肿瘤、肉瘤类等有较佳的疗效。为了寻找新的有效低毒药物,由南京大学配位化学研究所合成铂络合物新药,中山医学院肿瘤研究所进行动物实验研究。第一批4种新合成四价铂化合物具有显著抗瘤作用已经报告。为了比较各药抗瘤活性及毒性的差异,对各药进行更多还原

【Abstract】 Eight platinum compounds were synthesized in the Institute of Ccordinate Compounds, Nanking University, they are: Dihydroxy-malonyl-diamine Platinum [Pt (NH3)2 (mal) (OH)2] ( Ⅰ ); Dihydroxy-malonyl-ethylendiamine platinum [Pt (en) (mal) (OH)2] ( Ⅱ ); Dihydroxy-oxalyl-ethylendiamine platinum [Tt (en) (C2O4) (OH)2 (Ⅲ); Dihydroxy-dibromc-ethylendiaminc platinum (Pt (en) Br2 (OH)2] ( Ⅳ ); Dihydroxy-cis-dichloro-diamine platinum [Pt (NH3)2 Cl2 (OH)2] ( Ⅴ ); Cis Dichlorc-diaminc platinum CCis-Pt (NH3)2 C12] (Ⅵ ); Malcnyl-ethy lendiamine platinum [Pt (en) (mal)] (Ⅶ); Malonyl-diamine platinum [Pt (NH3)2 (mal)] (Ⅷ).These compounds were shown to have significant antitumor activities against W-256 carcinosarcoma in rats. Their inhibition rates were ( Ⅰ ): 99.5~100%, ( Ⅱ ): 98.3~99.8%; (Ⅲ) 61~98.3%; (Ⅳ)99.5-100%; (Ⅴ)99.69~100%; (Ⅳ)98.5%~99.39; (Ⅶ)99.2~ 99.8%;(Ⅷ)99.18~100%; respectively, with high tumor regression rates from 5/10 to 10/10. The 95-day follow-up of the regressed tumors showed, that except in individual rats with relapsing, in most rats the regressed tumors did not recur.The dose-effect relationship of the first 6 compounds were studied in W-256 tumor, and showed that the 90% cure dose (CD90) of compound ( Ⅰ ) was 21.2 mg/kg/D × 7; 90% inhibition dose (ID90) of ( Ⅰ ) was 12.5 mg/kg/D × 7; ID90 of (Ⅱ) was 17 mg/kg/D × 7; ID90 of (Ⅲ)was 14.5 mg/kg/D × 7; ID90 of (Ⅳ) was 4.8 mg/kg/D × 7:. ID90 of (Ⅴ) 2.38 mg/kg/D × 7; ID90 of (Ⅵ) was 0.21 mg/kg/D×7. The abovementioned data showed that the tolerated doses for aminals and also the antitumor doses of chelated platinum compounds, such as compounds ( Ⅰ ) and ( Ⅱ ) were higher; whereas these doses of non-chelated platinum compounds such as (Ⅵ) were lower. This may be attributed to the lower dissociation rate of the chelated compounds and to the less active substances formed.更多还原