Design, synthesis, in vitro acetylcholinesterase, butyrylcholinesterase activities, and in silico molecular docking study of oxindole-oxadiazole hybrid analogues

被引:7
作者
Alzahrani, Abdullah Yahya Abdullah [1 ]
Ullah, Hayat [2 ]
Bhat, Mashooq Ahmad [3 ]
Rahim, Fazal [4 ]
Al-Wesabi, Esam Omar [5 ]
Alanazi, Tahani Y. A. [6 ]
机构
[1] King Khalid Univ, Fac Sci & Arts, Dept Chem, Mohail Assir, Saudi Arabia
[2] Univ Okara, Dept Chem, Okara 56130, Pakistan
[3] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh 11451, Saudi Arabia
[4] Hazara Univ, Dept Chem, Mansehra 21300, KP, Pakistan
[5] Hodeidah Univ, Hodeidah, Yemen
[6] Univ Hail, Coll Sci, Dept Chem, Hail 81451, Saudi Arabia
关键词
Oxindole; Oxadiazole; Acetylcholinesterase; Butyrylcholinesterase; Molecular docking; ALZHEIMERS-DISEASE; DERIVATIVES; INHIBITORS; POTENT;
D O I
10.1016/j.molstruc.2023.137167
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Alzheimer's disease is a neurological disorder characterized by cognitive dysfunction and deficits in activities of daily living. There is no drug available for Alzheimer's at the moment, and the inhibition of acetylcholinesterase and butyrylcholinesterase enzymes are a good target to treat Alzheimer's disease. In this study, a series of new oxindole-oxadiazole hybrid analogues (1-18) have been synthesized and evaluated for acetylcholinesterase and butyrylcholinesterase inhibitory activities. All compounds showed a varied degree of inhibition, ranging from 0.80 +/- 0.20 to 12.50 +/- 0.40 mu M (against acetylcholinesterase) and 1.10 +/- 0.20 to 20.30 +/- 0.10 mu M (against butyrylcholinesterase), as compared to the standard inhibitor donepezil (IC50 values of 2.16 +/- 0.12 & 4.5 +/- 0.11 mu M, respectively). In the case of acetylcholinesterase, analogue 17 (IC50 = 0.80 +/- 0.20 mu M) while in case of butyrylcholinesterase, analogue 5 (IC50 = 1.10 +/- 0.20 mu M) was found the most potent among the whole series. Structure-activity relationship has been established for all compounds, which mainly depended upon the nature, number, position, and electron-donating or-withdrawing effect of the substituent(s) on the phenyl ring. A molecular docking study was carried out to investigate the interaction of the most potent compounds with the active site of enzymes. The stability of each drug-like hit in complex with acetylcholinesterase and butyrylcholinesterase was determined by computing their RMSD, RMSF analysis. Among all the compounds, compound 17 and compound 5 respectively, revealed a good interactions and stability during the entire simulation procedure.
引用
收藏
页数:14
相关论文
共 42 条
[1]  
Aarsland D, 2021, NAT REV DIS PRIMERS, V7, DOI 10.1038/s41572-021-00280-3
[2]   Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer's Disease along with Molecular Docking Study [J].
Adalat, Bushra ;
Rahim, Fazal ;
Rehman, Wajid ;
Ali, Zarshad ;
Rasheed, Liaqat ;
Khan, Yousaf ;
Farghaly, Thoraya A. ;
Shams, Sulaiman ;
Taha, Muhammad ;
Wadood, Abdul ;
Shah, Syed A. A. ;
Abdellatif, Magda H. .
PHARMACEUTICALS, 2023, 16 (02)
[3]   Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor [J].
Al-Karmalawy, Ahmed A. ;
Dahab, Mohammed A. ;
Metwaly, Ahmed M. ;
Elhady, Sameh S. ;
Elkaeed, Eslam B. ;
Eissa, Ibrahim H. ;
Darwish, Khaled M. .
FRONTIERS IN CHEMISTRY, 2021, 9
[4]   Biological activity of oxadiazole and thiadiazole derivatives [J].
Atmaram, Upare Abhay ;
Roopan, Selvaraj Mohana .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2022, 106 (9-10) :3489-3505
[5]   Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity [J].
Bhaskar, Gangaru ;
Arun, Yuvaraj ;
Balachandran, Chandrasekar ;
Saikumar, Chandrasekara ;
Perumal, Paramasivan T. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 51 :79-91
[6]   Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery [J].
Biernacki, Karol ;
Dasko, Mateusz ;
Ciupak, Olga ;
Kubinski, Konrad ;
Rachon, Janusz ;
Demkowicz, Sebastian .
PHARMACEUTICALS, 2020, 13 (06)
[7]   Comprehensive Review on Alzheimer's Disease: Causes and Treatment [J].
Breijyeh, Zeinab ;
Karaman, Rafik .
MOLECULES, 2020, 25 (24)
[8]  
Cacabelos Ramon, 2007, Neuropsychiatr Dis Treat, V3, P303
[9]   Role of Cholinergic Signaling in Alzheimer's Disease [J].
Chen, Zhi-Ru ;
Huang, Jia-Bao ;
Yang, Shu-Long ;
Hong, Fen-Fang .
MOLECULES, 2022, 27 (06)
[10]   Synthesis of azomethines derived from cinnamaldehyde and vanillin: in vitro aetylcholinesterase inhibitory, antioxidant and insilico molecular docking studies [J].
Chigurupati, Sridevi ;
Selvaraj, Manikandan ;
Mani, Vasudevan ;
Mohammad, Jahidul I. ;
Selvarajan, Kesavanarayanan K. ;
Akhtar, Shaikh S. ;
Marikannan, Maharajan ;
Raj, Suthakaran ;
Teh, Lay K. ;
Salleh, Mohd Z. .
MEDICINAL CHEMISTRY RESEARCH, 2018, 27 (03) :807-816