Total synthesis of Calebin-A, preparation of its analogues, and their neuronal cell protectivity against beta-amyloid insult.
A total synthesis of Calebin-A (1), a novel curcuminoid isolated from turmeric (Curcuma longa, Zingiberaceae) that has been demonstrated to protect neuronal cells from beta-amyloid insult, was successfully achieved in four steps. Elaborating on this synthetic route, 13 analogues were prepared for a structure-activity relationship (SAR) study. It was found that the parent compound 1 and derivatives 21, 28, and 30 protect PC12 rat pheocromocytoma and IMR-32 human neuroblastoma cells from beta-amyloid(25-35) insult. These results suggest that hydroxy group at para-position is most critical for the expression of biological activity.
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The Program for Collaborative Research in Pharmaceutical Science and the Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA. dshlkim@uic.edu
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D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001671:Biochemistry / Q000379:methods; D002934:Cinnamates; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D039821:Monoterpenes; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D002934:Cinnamates; D039821:Monoterpenes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C448819:calebin-A; D003474:Curcumin