Eliminating the heart from the curcumin molecule: monocarbonyl curcumin mimics (MACs).
Eliminating the heart from the curcumin molecule: monocarbonyl curcumin mimics (MACs).
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DOI：
10.3390/molecules20010249
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发表时间：
2014-12-24
期刊：
影响因子：
--
通讯作者：
Snyder JP
中科院分区：
文献类型：
--
作者：
Shetty D;Kim YJ;Shim H;Snyder JP
姜黄素是一种具有数千年历史的天然产物。其传统的亚洲应用于人类疾病，近几十年来已受到世界范围内的药理学，生物化学和临床研究。姜黄素的致命弱点在于其水溶性差，在pH约7.4时快速降解。研究人员试图通过化学操作来解锁姜黄素的资产。一类正在研究的分子是姜黄素的单羰基类似物（MAC）。一千多个这样的代理人已经创建和测试主要针对癌症和炎症。结果是显而易见的。在体外，对于许多癌细胞系和细胞蛋白质，MAC提供相对于姜黄素的10-20倍效力增益。类似地，与姜黄素相比，MAC已经成功地在小鼠中表现出更好的药代动力学（PK）特征，并且在体内癌症异种移植物中表现出更大的肿瘤消退。通过鼠体重增加和组织病理学评估测量，化合物显示有限的毒性。据我们所知，MAC成员尚未在大型动物或人类中进行监测。然而，第一阶段的临床试验肯定是在地平线上。本综述重点介绍了癌症和炎症领域的大量和不断发展的工作，但也涵盖了MAC结构多样性和早期发现用于治疗细菌，结核病，阿尔茨海默病和疟疾。
Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria.
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通讯作者：
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