Discovery of Tryptophan-tetrahydroisoquinoline Derivatives as Multifunctional Agents for Treatment of Alzheimer's Disease

被引：5
|
作者：
Lu, Xin [1 ]
Liu, Yijun [1 ]
Qin, Nan [3 ]
Du, Chenxi [1 ]
Hu, Yanyu [3 ]
Chen, Yao [2 ]
Sun, Haopeng [1 ]
机构：
[1] China Pharmaceut Univ, Sch Pharm, Nanjing 211198, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China
[3] China Pharmaceut Univ, Dept Nat Med Chem, Nanjing 211198, Jiangsu, Peoples R China
来源：
CHINESE JOURNAL OF CHEMISTRY | 2022年 / 40卷 / 15期
基金：
中国国家自然科学基金;
关键词：
Alzheimer's disease; Butyrylcholinesterase; Inhibitors; Molecular modeling; Biological activity; TARGET-DIRECTED LIGANDS; BUTYRYLCHOLINESTERASE; ACETYLCHOLINESTERASE; ANTIOXIDANT; INHIBITION; ANALOGS; DESIGN; POTENT; MODEL;
D O I：
10.1002/cjoc.202200096
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Comprehensive Summary The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease (AD). We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase (BChE) inhibitors. Molecular docking was applied for the rational design and binding mode analysis. They were defined according to their target inhibitory activity, low cytotoxicity, predicted permeability through the blood-brain barrier (BBB), and in vivo cognitive improvement. Additionally, the preferred compound showed ability to decrease self-induced A beta(1-42) aggregation and A beta(1-42) induced SH-SY5Y cell injury. Altogether, these factors indicated their potential as unique lead compounds for AD treatment.
引用
收藏
页码：1821 / 1830
页数：10
相关论文
共 50 条
  • [21] Design, synthesis and evaluation of novel bivalent β-carboline derivatives as multifunctional agents for the treatment of Alzheimer's disease
    Zhao, Yifan
    Ye, Feng
    Xu, Jian
    Liao, Qinghong
    Chen, Lei
    Zhang, Weijia
    Sun, Haopeng
    Liu, Wenyuan
    Feng, Feng
    Qu, Wei
    BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (13) : 3812 - 3824
  • [22] Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease
    Makhaeva, Galina F.
    Grishchenko, Maria V.
    Kovaleva, Nadezhda V.
    Boltneva, Natalia P.
    Rudakova, Elena V.
    Astakhova, Tatiana Y.
    Timokhina, Elena N.
    Pronkin, Pavel G.
    Lushchekina, Sofya V.
    Khudina, Olga G.
    Zhilina, Ekaterina F.
    Shchegolkov, Evgeny V.
    Lapshina, Maria A.
    Dubrovskaya, Elena S.
    Radchenko, Eugene V.
    Palyulin, Vladimir A.
    Burgart, Yanina V.
    Saloutin, Victor I.
    Charushin, Valery N.
    Richardson, Rudy J.
    ARCHIV DER PHARMAZIE, 2025, 358 (01)
  • [23] Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment
    Zheng, Yunxiaozhu
    Qiang, Xiaoming
    Xu, Rui
    Song, Qing
    Tian, Chaoquan
    Liu, Hongyan
    Li, Wei
    Tan, Zhenghuai
    Deng, Yong
    BIOORGANIC CHEMISTRY, 2018, 78 : 298 - 306
  • [24] Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease
    Xu, Yi-xiang
    Wang, Huan
    Li, Xiao-kang
    Dong, Sheng-nan
    Liu, Wen-wen
    Gong, Qi
    Wang, Tian-duan-yi
    Tang, Yun
    Zhu, Jin
    Li, Jian
    Zhang, Hai-yan
    Mao, Fei
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 143 : 33 - 47
  • [25] Recent Advances in the Synthesis of Tacrine Derivatives as Multifunctional Agents for Alzheimer's Disease
    Liang W.
    Min L.-J.
    Han L.
    Liu X.-H.
    Current Organic Chemistry, 2021, 25 (23) : 2840 - 2855
  • [26] Recent Advances in the Synthesis of Tacrine Derivatives as Multifunctional Agents for Alzheimer's Disease
    Ahmed, Ikram Baba
    Kibou, Zahira
    Choukchou-Braham, Noureddine
    CURRENT ORGANIC CHEMISTRY, 2021, 25 (21) : 2579 - 2624
  • [27] Naturally Inspired Molecules as Multifunctional Agents for Alzheimer's Disease Treatment
    Rampa, Angela
    Tarozzi, Andrea
    Mancini, Francesca
    Pruccoli, Letizia
    Di Martino, Rita Maria Concetta
    Gobbi, Silvia
    Bisi, Alessandra
    De Simone, Angela
    Palomba, Francesco
    Zaccheroni, Nelsi
    Belluti, Federica
    MOLECULES, 2016, 21 (05):
  • [28] Sulfonamides as multifunctional agents for Alzheimer's disease
    Bag, Seema
    Tulsan, Rekha
    Sood, Abha
    Cho, Hyejin
    Redjeb, Hana
    Zhou, Weihong
    LeVine, Harry, III
    Toeroek, Bela
    Toeroek, Marianna
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (03) : 626 - 630
  • [29] Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease
    Leng, Jing
    Qin, Hua-Li
    Zhu, Kaicheng
    Jantan, Ibrahim
    Hussain, Muhammad Ajaz
    Sher, Muhammad
    Amjad, Muhammad Wahab
    Naeem-ul-Hassan, Muhammad
    Ahmad, Waqas
    Bukhari, Syed Nasir Abbas
    CHEMICAL BIOLOGY & DRUG DESIGN, 2016, 88 (06) : 889 - 898
  • [30] Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
    Sang, Zhi-pei
    Qiang, Xiao-ming
    Li, Yan
    Wu, Bei
    Zhang, Hui
    Zhao, Ming-gao
    Deng, Yong
    CHEMICAL BIOLOGY & DRUG DESIGN, 2015, 86 (05) : 1168 - 1177
12345