2-(1-羟基)乙基二氢卟吩f及其醚衍生物对小鼠肉瘤180移植瘤的光化学治疗作用

Photochemotherapeutic Effects of 2-(1-Hydroxyl)ethyl Chlorin f and Its Ether Derivatives on Sarcoma 180 Transplanted in Mice

目的 探讨 2 (1 羟基 )乙基二氢卟吩f(3a)及其醚衍生物 (4b、4c、4d)对小鼠肉瘤 180移植瘤的光化学治疗作用。方法 雄性小鼠前胸皮下接种肉瘤 180 ,待肿瘤生长至直径为 6～ 8mm时 ,按体重和瘤径随机分成 6组 ,每组 8～ 10只。实验小鼠尾静脉注射给药 (3a、4b、4c和HpD组剂量均为 5mg kg,4d组为 2 5mg kg) 15min后用溴化亚铜蒸气 染料激光 (6 30nm)垂直照射瘤区 2 0min ,功率密度 15 0mW cm2 ,光斑直径 1 5cm ,能量密度 180J cm2 ,光照后肿瘤完全消失 ,并在 30天内不复发作为治愈。结果 3a、4b、4c、4d及HpD组的治愈小鼠数与实验小鼠数的比率分别为 0 10 ,6 8,8 9,10 10 ,2 10。 4b、4c、4d对小鼠肉瘤 180移植瘤的光化学治疗效果均优于参比药物血卟啉衍生物 (HpD) ,其中 ,又以 4d的疗效最强 ;而 3a无效。结论 2 (1 羟基 )乙基二氢卟吩f醚衍生物对小鼠肉瘤 180移植瘤的光化学治疗效果 ,随醚链增长而增强 ,这对我们今后进一步的构效关系研究具有重要的意义。

Objective A new type of photosensitizer, 2-(1-hydroxy) ethyl chlorin f(3a) and its ether derivatives (4b, 4c, 4d), made from chlorophyll of silkworm excrement, has been developed in our department. The purpose of this study is to evaluate the photochemotherapeutic effects of those compounds on sarcoma 180 transplanted in mice. Methods Subcutaneous inoculation of sarcoma 180 was made on the forechest of male mice. When the tumors reached 6～8 mm in diameter, the tumor-transplanted mice were randomly divided into 6 groups according to weight and diameter of tumor, 8～10 mice each group. Tumors were irradiated vertically with 630nm (CuBr vapor-dye laser) for 20 min at a power density of 150 mW/cm 2〔spot diameter:1 5 cm, energy density(ED):180 J/cm 2〕 at 15 min after intravenous injection in a dose of 5 mg/kg of 3a, 4b, 4c as well as HpD, 2 5 mg/kg of 4d, respectively. The tumor-transplanted mice were considered to be cured only when the tumors disapear completely after light irradiation and do not recur within 30 days.Results The ratios between the cured mice and the tested mice in the 3a, 4b, 4c, 4d as well as HpD groups were 0/10, 6/8, 8/9, 10/10 and 2/10, respectively. The above described results of preliminary experiment showed that 4b, 4c and 4d have more efficacious photochemotherapeutic potency than that of HpD, and 4d is the best among them, but 3a has no photochemotherapeutic potency. Conclusions The photochemotherapeutic potency of 2-(1-hydroxyl)ethyl chlorin f ether derivatives on sarcoma 180 trans-planted in mice enhanced as their chain length increased. Further studies on their structure-action-relationship seem to be of importance as well.