苯并异硒唑酮磺酰胺衍生物对环氧酶的抑制作用

INHIBITORY EFFECTS OF BENZOISOSELENOTHIAZOLIDONE SULFONAMIDE DERIVATIVES ON CYCLOOXYGENASE

目的 研究苯并异硒唑酮磺酰胺衍生物对环氧酶的抑制作用。方法 放免法 ;RT PCR法。结果 化合物A和B对COX 1和COX 2的代谢产物TXB2和PGE2的IC50 比值分别为 10 0 0和 5 6 0 ,化合物A和B可抑制LPS诱导的大鼠腹腔巨噬细胞COX 2mRNA生成 ,而对COX 1的mRNA生成无影响。结论 化合物A和B为COX 2选择性抑制剂 ,可抑制COX

AIM To study the inhibitory effects of benzoisoselenothiazolidone sulfonamide derivatives on cyclooxygenase. METHODS 6 Keto PGF 1α and PGE 2 were assayed by radioimmunoassay (RIA) method; mRNA expression of COX 1 and COX 2 were assayed by reverse transcription ploymerase chain reaction (RT PCR) method. RESULTS Compound A [ N 4 (4 methoxyphenyl aminosulfonyl) benzoisoselenothiazolidone] and B [ N 4 (4 fluorophenyl aminosulfonyl) benzoisoselenothiazolidone] were two benzoisoselenothiazolidone sulfonamide derivatives, which can inhibit COX activity with IC 50 of 1 5×10 -8 mol·L -1 and 5 0×10 -8 mol·L -1 for COX 2, as well as IC 50 of 1 5×10 -5 mol·L -1 and 2 8×10 -5 mol·L -1 for COX 1. The ratio of IC 50 COX 1 /IC 50 COX 2 of compound A and B are 1 000 and 560, respectively. They both can inhibit COX 2 mRNA expression in cultured rat peritoneal macrophages stimulated with LPS (1 μg·mL -1 ), and have no effect on COX 1 mRNA expressions. CONCLUSION Compound A and B, two benzoisoselenothiazolidone sulfonamide derivatives, both are selective inhibitory agents of COX 2, and possess inhibitory effects on 5 lipoxygenase and cyclooxygenase.