Pyrazolines as potential anti-Alzheimer's agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies

被引：3
作者：
Machado, Valkiria [1 ]
Cenci, Arthur R. [1 ]
Teixeira, Kerolain F. [1 ]
Sens, Larissa [2 ]
Tizziani, Tiago [2 ]
Nunes, Ricardo J. [2 ]
Ferreira, Leonardo L. G. [3 ]
Yunes, Rosendo A. [2 ]
Sandjo, Louis P. [2 ]
Andricopulo, Adriano D. [3 ]
de Oliveira, Aldo S. [1 ]
机构：
[1] Univ Fed Santa Catarina, Dept Exact Sci & Educ, Rua Joao Pessoa 2514 Bairro Velha, BR-89036004 Blumenau, SC, Brazil
[2] Univ Fed Santa Catarina, Dept Chem, Florianopolis, SC, Brazil
[3] Univ Sao Paulo, Inst Phys Sao Carlos, Ctr Res & Innovat Biodivers & Drug Discovery, Sao Carlos, SP, Brazil
来源：
RSC MEDICINAL CHEMISTRY | 2022年 / 13卷 / 12期
关键词：
ACETYLCHOLINESTERASE; DERIVATIVES;
D O I：
10.1039/d2md00262k
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Alzheimer's disease (AD) is a neurodegenerative disease that is characterized as the main dementia in the elderly. Eighteen pyrazolines were synthesized and evaluated for their inhibitory effects against acetylcholinesterase (AChE) in vitro. Possible interactions between pyrazolines and the enzyme were explored by in silico experiments. Compound 2B of the series was the most active pyrazoline with an IC50 value of 58 nM. Molecular docking studies revealed two important pi-pi interactions with residues Trp 286 and Tyr 341. A correlation between the HOMO-1 surface and AChE inhibition was observed. ADMET assays demonstrated a good profile for compound 2B. From the abovementioned findings, a new avenue of compound 2B analogues could be explored to develop anti-AD agents.
引用
收藏
页码：1644 / 1656
页数：13
相关论文
共 50 条
  • [31] Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents
    Salehi, Naeimeh
    Mirjalili, Bi Bi Fatemeh
    Nadri, Hamid
    Abdolahi, Zahra
    Forootanfar, Hamid
    Samzadeh-Kermani, Alireza
    Kucukkilinc, Tuba Tuylu
    Ayazgok, Beyza
    Emami, Saeed
    Haririan, Ismaeil
    Sharifzadeh, Mohammad
    Foroumadi, Alireza
    Khoobi, Mehdi
    BIOORGANIC CHEMISTRY, 2019, 83 : 559 - 568
  • [32] Carbamate as a potential anti-Alzheimer's pharmacophore: A review
    Singh, Yash Pal
    Kumar, Navneet
    Chauhan, Brijesh Singh
    Garg, Prabha
    DRUG DEVELOPMENT RESEARCH, 2023, 84 (08) : 1624 - 1651
  • [33] Hybrid benzothiazole derived fused triazole/thiazole derivatives as versatile anti-Alzheimer agents: synthesis, characterization, biological evaluation and molecular docking studies
    Khan, Shoaib
    Hussain, Rafaqat
    Khan, Yousaf
    Iqbal, Tayyiaba
    Chinnam, Sampath
    Akif, Muhammad
    Dera, Ayed A.
    JOURNAL OF MOLECULAR STRUCTURE, 2024, 1318
  • [34] Design, Synthesis, in vitro biological evaluation and in silico molecular docking study of chloro substituted Benzimidazole-Thiazole hybrid derivatives as potential Anti-Alzheimer ' s agents
    Kaleem, Sana
    Ullah, Hayat
    Nabi, Muhammad
    Hussain, Rafaqat
    Khan, Shoaib
    Sajid, Muhammad
    Iqbal, Naveed
    Rahim, Fazal
    Iqbal, Tayyiaba
    Hussain, Amjad
    Iqbal, Rashid
    Zahid, Zunaira
    Mohany, Mohamed
    Aghayeva, Saltanat
    RESULTS IN CHEMISTRY, 2024, 8
  • [35] Novel sarsasapogenin-triazolyl hybrids as potential anti-Alzheimer's agents: Design, synthesis and biological evaluation
    Wang, Wenbao
    Wang, Wei
    Yao, Guodong
    Ren, Qiang
    Wang, Di
    Wang, Zedan
    Liu, Peng
    Gao, Pinyi
    Zhang, Yan
    Wang, Shaojie
    Song, Shaojiang
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 151 : 351 - 362
  • [36] DFT Study of Regio- and Stereoselective 13DC Reaction between Diazopropane and Substituted Chalcone Derivatives: Molecular Docking of Novel Pyrazole Derivatives as Anti-Alzheimer's Agents
    Al-Hazmy, Sadeq M.
    Zouaghi, Mohamed Oussama
    Amri, Nasser
    Arfaoui, Youssef
    Alhagri, Ibrahim A.
    Hamdi, Naceur
    MOLECULES, 2023, 28 (04):
  • [37] Synthesis, Docking and Acetylcholinesterase Inhibitory Evaluation of 1,3,4-Thiadiazole Derivatives as Potential Anti-Alzheimer Agents
    Mohammadi-Farani, Ahmad
    Takesh, Milad
    Mohammadi, Mahsa
    Hosseini, Amin
    Aliabadi, Amin
    Aliabadi, Alireza
    PHARMACEUTICAL SCIENCES, 2024, 30 (03) : 369 - 378
  • [38] Synthesis, biological and computational evaluation of benzoxazole hybrid analogs as potential anti-Alzheimer's agents
    Othman, Mohamed S.
    Hussain, Rafaqat
    Rahim, Fazal
    Ullah, Hayat
    Khan, Shoaib
    Taha, Muhammad
    Fareid, Mohamed A.
    Altaleb, Anas T.
    Aboelnaga, Shimaa M.
    Shah, Syed Adnan Ali
    FUTURE MEDICINAL CHEMISTRY, 2024, 16 (19) : 2013 - 2023
  • [39] De-novo Drug Design, Molecular Docking and In-Silico Molecular Prediction of AChEI Analogues through CADD Approaches as Anti-Alzheimer's Agents
    Pandey, Surabhi
    Singh, B. K.
    CURRENT COMPUTER-AIDED DRUG DESIGN, 2020, 16 (01) : 54 - 72
  • [40] Medicinal perspectives, molecular docking and structure activity relationship of benzothiazole derived thiazole-based bis-benzohydrazide as potential anti-Alzheimer agents
    Khan, Shoaib
    Dera, Ayed A.
    Hussain, Rafaqat
    Iqbal, Tayyiaba
    Khan, Yousaf
    Ahmad, Zia
    Ullah, Farman
    Hussain, Amjad
    RESULTS IN CHEMISTRY, 2024, 10
12345