title: Curcumin derivatives inhibit or modulate beta-amyloid precursor protein metabolism.
abstract: Curcumin-derived oxazoles and pyrazoles were synthesized in order to minimize the metal chelation properties of curcumin. The reduced rotational freedom and the absence of stereoisomers was anticipated to enhance the inhibition of gamma-secretase. Accordingly, the replacement of the 1,3-dicarbonyl moiety by isosteric heterocycles turned curcumin analogue oxazoles and pyrazoles into potent gamma-secretase inhibitors. Compounds 4a-i were found to be potent inhibitors of gamma-secretase and displayed activity in the low micromolar range.
authors.affiliation: Clemens Schöpf-Institute of Chemistry and Biochemistry, Darmstadt University of Technology, Darmstadt, Germany.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Narlawar
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Baumann
authors.forename: Robert
authors.initials: R
authors.lastname: Schubenel
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans
chemical_list: D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D003474:Curcumin