ENZYME INHIBITORS AS PROTENTIAL ANTICANCER AND ANTIVIRAL DRUGS

碱催化分解泽布拉林的反应机理研究 类似的2-氧代嘧啶核苷已被完全阐明。这个 以前难以捉摸的亲电物种是在 分解后的药物(S)已鉴定为丙二醛。 丙二醛是一种非常活跃的物种，能够与 核酸。这一现象与抗肿瘤作用的相关性 目前正在对ZeBularine及其类似物进行研究。 一些独特的五元环伽马-内酯被替换为 肉豆蔻酸酯基或油酸酯基团在生物学上被发现 相当于内源性蛋白激酶C(PK-C)激动剂 甘油二酯(DAG)。这些化合物具有固定的构象， 被推定为类似于DAG采用的构象 绑定PK-C。这些伽马-内酯的两个长烷基醚类似物 也表现为良好的DAG代理。这些化合物具有优势 具有稳定的水解性。根据这些线索，第二个 合成了刚性DAG类似物。生物学 对这些新化合物的评估正在进行中。

The mechanism of the base-catalyzed decomposition of zebularine and similar 2-oxopyrimidine nucleosides has been completely elucidated. The previously elusive electrophilic species generated during the decomposition of the drug(s) has been identified as malonaldehyde. Malonaldehyde is a very reactive species capable of interacting with nucleic acids. The relevance of this phenomenon to the antitumor effect of zebularine and its analogues is under investigation. Some unique five-membered ring gamma-lactones substituted with either myristic or oleic acid ester groups were found to be biologically equivalent to the endogenous protein kinase-C (PK-C) agonist diacylglycerol (DAG). These compounds have a fixed conformation which is presumed to be similar to the conformation adopted by DAG when binding to PK-C. Two long alkyl-ether analogues of these gamma-lactones behaved also as good DAG surrogates. These compounds have the advantage of being hydrolytically stable. Based on these leads, a second generation of rigid DAG analogues was synthesized. Biological evaluation of these new compounds is in progress.