Curcumin derivatives inhibit or modulate beta-amyloid precursor protein metabolism.
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.
Narlawar
Rajeshwar
R
Clemens Schöpf-Institute of Chemistry and Biochemistry, Darmstadt University of Technology, Darmstadt, Germany.
Baumann
Karlheinz
K
Schubenel
Robert
R
Schmidt
Boris
B
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
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D003474:Curcumin