Center for Self-assembly and Complexity, Institute for Basic Science, Pohang 790-784, Korea.
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Molecules. 2014 Dec 24;20(1):249-92. doi: 10.3390/molecules20010249.
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.
姜黄素是一种具有几千年历史的天然产物。近几十年来，其在亚洲传统上用于治疗人类疾病的应用已在世界范围内进行了药理学、生物化学和临床研究。姜黄素的弱点在于其在 pH 值为~7.4 时的水中溶解度差和快速降解。研究人员试图通过化学修饰来挖掘姜黄素的潜力。受到关注的一类分子是姜黄素的单羰基类似物（MACs）。已经创造并测试了超过 1000 种此类化合物，主要针对癌症和炎症。结果很明确。在体外，MACs 对许多癌细胞系和细胞蛋白的效力比姜黄素提高了 10-20 倍。同样，MACs 在小鼠中的药代动力学（PK）谱和体内肿瘤异种移植中的肿瘤消退方面表现出更好的效果，优于姜黄素。这些化合物的毒性有限，这可以通过小鼠体重增加和组织病理学评估来衡量。据我们所知，MAC 成员尚未在较大的动物或人类中进行监测。然而，第一阶段临床试验肯定迫在眉睫。本综述重点介绍了在癌症和炎症方面的大量且不断发展的工作，但也涵盖了 MAC 的结构多样性以及用于治疗细菌、结核病、阿尔茨海默病和疟疾的早期发现。
