The Tunable Functionality of α,β-Unsaturated Carbonyl Compounds Enables Their Differential Application in Biological Systems
The Tunable Functionality of α,β-Unsaturated Carbonyl Compounds Enables Their Differential Application in Biological Systems
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DOI：
10.1002/cmdc.200900499
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发表时间：
2010-03-01
期刊：
影响因子：
3.4
通讯作者：
Amslinger, Sabine
中科院分区：
文献类型：
--
作者：
Amslinger, Sabine
α，β-不饱和羰基化合物作为潜在的药物候选物是一个有争议的话题，因为它们潜在的迈克尔受体活性可导致细胞损伤和细胞毒性。然而，α，β-不饱和羰基官能团可以用作通过直接操纵该实体来微调生物活性的工具。根据它们的电子性质，α，β-不饱和羰基官能团显示出不同的反应性，即迈克尔加成、自由基清除、氧化或双键异构化。修饰α，β-不饱和羰基系统的α-位置，这是一个尚未被广泛探索的概念，可以产生新的，非常有趣的衍生物。目前在药物开发中，活性位点的不可逆结合已被证明是癌症治疗中耐药性的一个答案。总的来说，含有α，β-不饱和羰基单元的天然产物具有多种生物活性，可以转化为新的药物制剂。
alpha,beta-Unsaturated carbonyl compounds as potential drug candidates is a controversial topic since their potential Michael acceptor activity can lead to cell damage and cytotoxicity. Nevertheless, the alpha,beta-unsaturated carbonyl functionality can be employed as a tool to fine tune biological activity by directly manipulating this entity. Depending on their electronic properties, alpha,beta-unsaturated carbonyl functionalities display different reactivities, namely Michael addition, radical scavenging, oxidation or double bond isomerization. Modifying the alpha-position of the alpha,beta-unsaturated carbonyl system, a concept that has not been widely explored, could produce new, very interesting derivatives. Currently in drug development, irreversible binding in active sites has proven to be one answer to drug resistance in cancer treatment. Overall, natural products containing the alpha,beta-unsaturated carbonyl unit possess multiple biological activities that could be transferred into novel pharmaceutical agents.