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7065924 
Journal Article 
Benzenediol-berberine hybrids: Multifunctional agents for Alzheimer's disease 
Jiang, H; Wang, Xu; Huang, L; Luo, Z; Su, Tao; Ding, Ke; Li, X; , 
2011 
Yes 
Bioorganic & Medicinal Chemistry
ISSN: 0968-0896
EISSN: 1464-3391 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
7228-7235 
22041172 
WOS:000296752300029 
We designed and synthesized a series of hybrid molecules, in an effort to identify novel multifunctional drug candidates for Alzheimer's disease (AD), by reacting berberine with benzenediol, melatonin, and ferulic acid. The products were evaluated for: (i) the ability to inhibit multiple cholinesterases (ChEs); (ii) the capacity to prevent amyloid beta (A beta) aggregation; and (iii) antioxidant activity. All of the derivatives were better antioxidants, and inhibited A beta aggregation to a greater extent, than the lead compound, berberine. Two of the hybrids, in particular, have the potential to be excellent candidates for AD therapy: the berberine-pyrocatechol hybrid (compound 8) was a much better inhibitor of acetylcholinesterase (AChE) than unconjugated berberine (IC50: 0.123 vs 0.374 mu M); and the berberine-hydroquinone hybrid (compound 12) displayed high antioxidant activity, could inhibit AChE (IC50 of 0.460 mu M), and had the greatest ability to inhibit Ab aggregation. (C) 2011 Elsevier Ltd. All rights reserved.