Bis (Diamines) Cu and Zn Complexes of Flurbiprofen as Potential Cholinesterase Inhibitors: In Vitro Studies and Docking Simulations

Muhammad Jamil,Muhammad Ilyas Tariq,Maryam Bashir,Rizwan Ashraf,Humna Ellahi,Wei Xing Zhang,Changrui Lu,Nargis Sultana,Muhammad Fayyaz Ur Rehman,Fariha Kanwal

doi:10.3390/cryst11020208

Abstract

Alzheimer’s disease (AD) causes dementia and continuous damage to brain cells. Cholinesterase inhibitors can alleviate the condition by increasing communication between the nerve cells and reducing the risk of dementia. In an effort to treat Alzheimer’s disease, we synthesized flurbiprofen-based diamines (1,2 diaminoethane and 1,3 diaminopropane) Zn(II), Cu(II) metal complexes and characterized them by single-crystal X-ray analysis, NMR, (FT)-IR, UV-Vis, magnetic susceptibility, elemental analysis and conductivities measurements. Synthesized diamine metal complexes appeared in ionic forms and have distorted octahedral geometry based on conductivity studies, magnetic susceptibility and electronic studies. Single crystal X-ray diffraction analysis confirmed (2b) Cu(H2O)2(L1)2(L2)2 complex formation. Moreover, we tested all synthesized metal complexes against the cholinesterase enzyme that showed higher inhibition potential. In general, copper metal complexes showed higher inhibitory activities than simple metal complexes with flurbiprofen. These synthesized metal complexes may derive more effective and safe inhibitors for cholinesterases.

Highlights

Studies show that numerous disorders, including Alzheimer’s disease (AD), correlate with high cholinesterase activity
Cholesterol overexpression may lead to numerous disorders like ataxia, myasthenia gravis and Parkinson’s disease [4,5]
X-ray H-NMR, analysis, 1H-NMR, 13C-NMR. These metalThese complexes are ionic based on conductivity rearmaments and have distorted metal complexes are ionic based on conductivity rearmaments and have octahedral geometry based on electronic and magnetic susceptibility studies

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. 2.5 to 4.0 million elderly people suffer from Alzheimer’s disease (AD), manifested by long-term neurodegeneration, loss of neural functions and cognitive abilities that lead to death [1]. Studies show that numerous disorders, including AD, correlate with high cholinesterase activity. Cholinesterase belongs to the serine hydrolases family, consisting of acetylcholinesterase (AChE) and butyryl-cholinesterase (BChE) [2,3]. Many physiological processes have been controlled by cholinesterase in either a direct or indirect way. Cholesterol overexpression may lead to numerous disorders like ataxia, myasthenia gravis and Parkinson’s disease [4,5]. To combat and treat these disorders, researchers have been looking for synthetic and natural inhibitors of cholinesterase

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