耳壳藻内酯及其中间产物药理作用的研究

 目的研究合成耳壳藻内酯及其中间产物抗癌和抗菌活性效应，探讨化学合成高效海洋药物前导化合物的可能途径。方法采用MTT比色法体外分析合成化合物对LLC肺癌和H22肝癌细胞毒作用；小鼠肉瘤S₁₈₀体内移植，观察合成化合物体内抑瘤率作用。通过试管倍比稀释法测定合成化合物最低抑菌浓度(MIC)，评价其体外抗菌活性。结果(±)耳壳藻内酯-1体外均具有一定的肿瘤细胞杀灭作用，IC₅₀为5.5 ～9.4μg·mL^-1，其体内抑瘤率明显大于中间合成物(±)酮基内酯-5。(±)酮基内酯-5对革兰阳性球菌、金黄色葡萄球菌、肺炎球菌具有较明显的抗菌作用，MIC为3.75μg·mL^-1。而对革兰阴性大肠杆菌抗菌作用较弱，对绿脓杆菌无抗菌作用。结论 化学合成耳壳藻内酯有望成为新型的抗癌和抗感染药物,对这些活性成分的研究为今后海洋药用资源的开发和新药的研究提供一个新的方向。

Experimental study of pharmacological action of new synthetic compounds caulilide(±)-1 and lactone(±)-5

OBJECTIVE To study the relationship between the structures and pharmacological effects of the total synthesized compounds of caulilide(±)1 and lactone(±)5,and to provide some foundation for new anticancer and antibacterial agents. METHODS The cytotoxicity of caulilide(±)1 and lactone(±) 5 on H22 and LLC cell lines were tested by MTT colorimetric method.The anticancer efficacy was investigated by injecting them into mice respectively.The MICs of caulilide (±)1 and lactone (±)5 against Gram positive and Gram negative organisms were determined by two fold tube dilution method. RESULTS IC₅₀of caulilide (±)1 and lactone (±)5 were 5.5～9.4 μg·mL^-1.Caullide(±)1 showed significant anticancer activity.The MIC of lactone(±)5 against Gram positive organisms was 3.75 μg·mL^-1.Pseudomonas pyocyanca was not sensitive to caulilide(±)1 and lactone(±)5. CONCLUSION New synthetic compounds showed strong biological activities.This research is of prospective values in the development of new drugs and utilization of marine Peyssonnelia caulifera resources.