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
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