Fujita Y, Yaegashi T, Sawada S, Oyama H, Yoshimoto T, Tsuru D
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Biol Pharm Bull. 1995 May;18(5):648-52. doi: 10.1248/bpb.18.648.
A hydrolytic enzyme which catalyzes hydrolysis of the ester-linkage of a series of 17-O-acyl derivatives of 7-ethylcamptothecin-21-(2-dimethylamino)ethylamide [acyl derivatives of 22E] was purified from rat liver and its properties were characterized. It hydrolyzed the ester-linkage of all 22E derivatives tested as well as p-nitrophenyl acetate at pH 8-9 but had no effect on 7-ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11: irinotecan), unlike CPT-11 converting carboxylesterase, which was previously purified from rat serum [Tsuji T. et al., J. Pharmacobio-Dyn., 14, 341 (1991)]. The enzyme had no effect on either acetyl choline or butyrylcholine. It was inhibited by several organophosphorous compounds such as diisopropyl fluorophosphate (DFP), bis-(p-nitrophenyl)phosphate and paraoxon, but was insensitive to inhibitors specific for choline esterases. These results indicate that this liver esterase is clearly distinct from choline esterase and serum CPT-11 converting enzyme and is able to convert pro-drugs, O-acyl derivatives of 22E, to an antitumor agent.
从大鼠肝脏中纯化出一种水解酶，该酶可催化7-乙基喜树碱-21-（2-二甲氨基）乙酰胺的一系列17-O-酰基衍生物[22E的酰基衍生物]的酯键水解，并对其性质进行了表征。在pH 8-9条件下，它能水解所有测试的22E衍生物以及对硝基苯乙酸的酯键，但对7-乙基-10-[4-（哌啶基）-1-哌啶基]羰基氧基喜树碱（CPT-11：伊立替康）没有影响，这与先前从大鼠血清中纯化的CPT-11转化羧酸酯酶不同[Tsuji T.等人，《药物生物动力学杂志》，14，341（1991）]。该酶对乙酰胆碱或丁酰胆碱均无作用。它受到几种有机磷化合物的抑制，如二异丙基氟磷酸酯（DFP）、双（对硝基苯基）磷酸酯和对氧磷，但对胆碱酯酶特异性抑制剂不敏感。这些结果表明，这种肝脏酯酶与胆碱酯酶和血清CPT-11转化酶明显不同，并且能够将前体药物22E的O-酰基衍生物转化为抗肿瘤剂。
