Department of Applied Biology and Chemical Technology and the Open Laboratory for Chiral Technology, The Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, P.R. China.
Int J Mol Med. 2010 Oct;26(4):447-55. doi: 10.3892/ijmm_00000484.
Curcumin (diferuloylmethane) is the main active ingredient of turmeric, a traditional herbal medicine and food of south Asia. Curcumin has been found to have a wide range of biological activities, including antioxidant, anti-inflammatory, chemopreventive and chemotherapeutic activities. Curcumin is currently being tested in clinical trials for treatment of various types of cancers, including multiple myeloma, pancreatic cancer and colon cancer. Although no toxicity associated with curcumin (even at very high doses) has been observed, the effects of curcumin in other solid tumors have been modest, primarily due to poor water solubility and poor bioavailability in tissues remote from the gastrointestinal tract. Therefore, there is a need for the discovery of curcumin analogs with better water solubility or greater bioavailability for the treatment of solid tumors such as prostate cancer. In this study, curcumin acetates and amino acid conjugates of curcumin were studied in terms of their proteasome inhibitory and antiproliferative effects against several human cancer cell lines. It was found that the water soluble amino acid conjugates of curcumin showed a potent antiproliferative effect and are potent proteasome inhibitors. Docking studies of the curcumin amino acid conjugates for proteasome inhibition were carried out to explain their biological activities. It is suggested that they may serve as the water soluble analogs of curcumin.
姜黄素（二芳基甲烷）是姜黄的主要活性成分，姜黄是南亚的一种传统草药和食品。姜黄素具有广泛的生物活性，包括抗氧化、抗炎、化学预防和化学治疗活性。姜黄素目前正在临床试验中用于治疗各种类型的癌症，包括多发性骨髓瘤、胰腺癌和结肠癌。尽管尚未观察到与姜黄素相关的毒性（即使在非常高的剂量下），但姜黄素对其他实体瘤的作用较为温和，主要是由于其在远离胃肠道的组织中的水溶性差和生物利用度低。因此，需要发现具有更好水溶性或更高生物利用度的姜黄素类似物，以治疗前列腺癌等实体瘤。在这项研究中，研究了姜黄素的乙酸盐和姜黄素的氨基酸缀合物，以评估它们对几种人类癌细胞系的蛋白酶体抑制作用和抗增殖作用。结果发现，姜黄素的水溶性氨基酸缀合物具有很强的抗增殖作用，是有效的蛋白酶体抑制剂。进行了姜黄素氨基酸缀合物对蛋白酶体抑制的对接研究，以解释其生物学活性。这些化合物可能作为姜黄素的水溶性类似物。
