title: Evaluation of curcumin acetates and amino acid conjugates as proteasome inhibitors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sheng Biao
authors.initials: SB
authors.lastname: Wan
authors.forename: Huanjie
authors.initials: H
authors.lastname: Yang
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qiuzhi Cindy
authors.initials: QC
authors.lastname: Cui
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kanwar
authors.forename: Imthiyaz
authors.initials: I
authors.lastname: Mohammad
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
authors.forename: Tak Hang
authors.initials: TH
authors.lastname: Chan
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011485:Protein Binding; D012995:Solubility
chemical_list: D000085:Acetates; D000596:Amino Acids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin
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