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Synthesis and biological evaluation of genistein‐ O ‐alkylamine derivatives as potential multifunctional anti‐Alzheimer agents
Author(s) -
Hong Chen,
Guo Huiyan,
Chen Shuai,
Lv Jianwu,
Zhang Xin,
Yang Yacheng,
Huang Kang,
Zhang Yijuan,
Tian Zhiyong,
Luo Wen,
Chen Yiping
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13414
Subject(s) - acetylcholinesterase , genistein , chemistry , aché , rivastigmine , cholinesterase , stereochemistry , combinatorial chemistry , enzyme , pharmacology , biochemistry , donepezil , biology , medicine , dementia , disease , pathology , endocrinology
A series of genistein derivatives were synthesized and evaluated as multifunctional anti‐Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC 50 value (0.034 μM) much lower than that of rivastigmine (6.53 μM). A Lineweaver–Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal‐chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 μM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.