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Novel hybrids of oxoisoaporphine-tryptamine as acetylcholinesterase-induced β-amyloid aggregation inhibitors with improved antioxidant properties

Zhao Hai-Tao (School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guilin, P.R. China)
Zhong Shu-Ming (School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guilin, P.R. China)
Qin Jiang-Ke (School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guilin, P.R. China)
Tang Huang (School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guilin, P.R. China)

A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced b-amyloid (Ab) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tryptamine or its derivative, connected through a a,w - alkyldiamide bridge. These hybrids exhibit moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity toward the AChE-induced Ab aggregation. Moreover, six out of the nine hybrids of this series exhibit a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.

Keywords: Alzheimer’s disease, acetylcholinesterase inhibitor, Ab antiag-gregating activity, oxoisoaporphine-tryptamine