柳珊瑚酸构效关系研究

Relationship between the structure and effect of suberogorgin

目的：初步研究柳珊瑚酸（Ｓｕｂ）的羧基与其生理活性的关系。方法：Ｓｕｂ酰化合成Ｎ丁基柳珊瑚酰胺（ＮＢＳ），Ｎ环己基柳珊瑚酰胺（ＮＣＳ）和Ｎ柳珊瑚酰ＮＮ二环己基脲（ＳＤＵ）；制备人红细胞膜和小鼠脑提取物作为乙酰胆碱酯酶（ＡＣｈＥ）的组织样品，比色法测定ＡＣｈＥ活力。结果：３种衍生物的收率分别为９０％，９２％和９０％。上述４种化合物抑制人红细胞膜ＡＣｈＥ的ｐＩ５０（抑制酶活力５０％的药物摩尔浓度的负对数）分别为４．９２，２．７９，２．７８和４．８７，抑制小鼠脑ＡＣｈＥ的ｐＩ５０分别为４．２２，２．１８，２．１７和４．１９；对小鼠的ＬＤ５０分别为２３．６，９６．０，８４．０，３５．８ｍｇ·ｋｇ－１。

OBJECTIVE:To initially investigate the relationship between the carboxyl and physiological effect of suberogorgin(Sub).METHODS:N butyl suberogorgamide(NBS),N cyclohexyl suberogorgamide(N CS),and N suberogorgamide N N dicyclohexyl urea(SDU) were synthetized.Human RBC membrane and mice brain extract were prepared as tissue samples of acetylcholinesterase(AChE).The activity of AChE was determined with colorimetry.RESULTS:Four compounds dose dependently inhibited AChE,with pI 50 (negative logarithm of molar concentration causing 50% inhibition of AChE)4.92,2.79,2.78,and 4.87 in human RBC,and 4.22,2.18,2.17,and 4.19 in mice brain,respectively.Their LD 50 in mice iv were separately 23.6,96.0,84.0,and 35.8 mg·kg -1 .CONCLUSION:The carboxyl of Sub was closely related to its activity and toxicity.