Hybrids of oxoisoaporphine-tacrine congeners: Novel acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation inhibitors

被引:67
作者
Tang, Huang [1 ]
Zhao, Li-Zhen [1 ]
Zhao, Hao-Tao [1 ]
Huang, Shi-Liang [2 ]
Zhong, Shu-Ming [1 ]
Qin, Jiang-Ke [1 ]
Chen, Zhen-Feng [1 ]
Huang, Zhi-Shu [2 ]
Liang, Hong [1 ]
机构
[1] Guangxi Normal Univ, Sch Chem & Chem Engn, State Key Lab Cultivat Base Chem & Mol Engn Med R, Guilin 541004, Peoples R China
[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Oxoisoaporphine derivatives; Synthesis; Acetylcholinesterase inhibitors; beta-amyloid aggregation; TARGET-DIRECTED LIGANDS; ALZHEIMERS-DISEASE; CHOLINERGIC HYPOTHESIS; BBB PERMEABILITY; FIBRIL FORMATION; ACHE INHIBITORS; PERIPHERAL SITE; PAMPA-MODELS; BINDING; DERIVATIVES;
D O I
10.1016/j.ejmech.2011.08.002
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced, beta-amyloid (A beta) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tacrine or its congener, connected through an oligomethylene linker containing an amine group at variable position. These hybrids exhibit high AChE inhibitory activity with IC50 values in the nanomolar range in most cases. Moreover, five out of the 12 hybrids of this series, particularly those bearing a tetrahydroacridine moiety, exhibit a significant in vitro inhibitory activity toward the AChE-induced and self-induced A beta aggregation, which makes them promising anti-Alzheimer drug candidates. (C) 2011 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:4970 / 4979
页数:10
相关论文
共 50 条
  • [1] Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation
    Tang, Huang
    Zhao, Hai-Tao
    Zhong, Shu-Ming
    Wang, Zhi-Yu
    Chen, Zhen-Feng
    Liang, Hong
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (06) : 2257 - 2261
  • [2] Novel hybrids of oxoisoaporphine-tryptamine as inhibitors of acetylcholinesterase-induced β-amyloid aggregation with improved antioxidant properties
    Zhao, Hai-Tao
    Zhong, Shu-Ming
    Qin, Jiang-Ke
    Tang, Huang
    JOURNAL OF THE SERBIAN CHEMICAL SOCIETY, 2015, 80 (02) : 127 - 136
  • [3] Benzophenone-based derivatives: A novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation
    Belluti, Federica
    Bartolini, Manuela
    Bottegoni, Giovanni
    Bisi, Alessandra
    Cavalli, Andrea
    Andrisano, Vincenza
    Rampa, Angela
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (05) : 1682 - 1693
  • [4] Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation
    Du, Hongtao
    Jiang, Xinyu
    Ma, Meng
    Xu, Huili
    Liu, Shuang
    Ma, Fang
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (24)
  • [5] New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors
    Kamil Zawada
    Kamila Czarnecka
    Małgorzata Girek
    Paweł Kręcisz
    František Trejtnar
    Jana Mandíková
    Jakub Jończyk
    Marek Bajda
    Mariusz Staśkiewicz
    Przemysław Wójtowicz
    Katarzyna Dziubek
    Robert Skibiński
    Paweł Szymański
    Chemical Papers, 2021, 75 : 249 - 264
  • [6] New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors
    Zawada, Kamil
    Czarnecka, Kamila
    Girek, Malgorzata
    Krecisz, Pawel
    Trejtnar, Frantisek
    Mandikova, Jana
    Jonczyk, Jakub
    Bajda, Marek
    Staskiewicz, Mariusz
    Wojtowicz, Przemyslaw
    Dziubek, Katarzyna
    Skibinski, Robert
    Szymanski, Pawel
    CHEMICAL PAPERS, 2021, 75 (01) : 249 - 264
  • [7] 4-Substituted sampangine derivatives: Novel acetylcholinesterase and β-myloid aggregation inhibitors
    Chen, Ke-Lin
    Gan, Ling
    Wu, Zhen-Hua
    Qin, Jin-Fang
    Liao, Wen-Xia
    Tang, Huang
    INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2018, 107 : 2725 - 2729
  • [8] Derivatives of oxoisoaporphine alkaloids: A novel class of selective acetylcholinesterase inhibitors
    Tang, Huang
    Ning, Fang-Xian
    Wei, Yong-Biao
    Huang, Shi-Liang
    Huang, Zhi-Shu
    Chan, Albert Sun-Chi
    Gu, Lian-Quan
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (13) : 3765 - 3768
  • [9] Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation
    Chen, Xinyu
    Wehle, Sarah
    Kuzmanovic, Natascha
    Merget, Benjamin
    Holzgrabe, Ulrike
    Koenig, Burkhard
    Sotriffer, Christoph A.
    Decker, Michael
    ACS CHEMICAL NEUROSCIENCE, 2014, 5 (05): : 377 - 389
  • [10] Multitarget-directed oxoisoaporphine derivatives: Anti-acetylcholinesterase, anti-β-amyloid aggregation and enhanced autophagy activity against Alzheimer's disease
    Wei, Shenqi
    Chen, Wei
    Qin, Jingfang
    Huangli, Yingzi
    Wang, Li
    Shen, Yue
    Tang, Huang
    BIOORGANIC & MEDICINAL CHEMISTRY, 2016, 24 (22) : 6031 - 6039