Original Articles
Mamdouh S. Masouda, Doaa . Gha
Abstract
The effect of some prepared cefepime metal complexes with Cr(III), Mn(II), Fe(III), Co(II), Cu(II), Zn(II), Cd(II), Hg(II) and mixed metals (Fe,Ni) or (Cu,Fe) on the activity and kinetics of purified acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B&A) were investigated. The brain AChE and MAO-A & B from Egyptian Mediterranean buffalo (Bas Buballus) was purified by ammonium sulphate precipitation, Sephadex G-25, and Sephadex G-100. The effect of these prepared metallo cefepime on the activity of pure AChE and also (MAO-B&A) were carried out in vitro by using standard colorimetric assays. The results revealed that AChE was inhibited by Mn(II) ,Cu(II) with different molar ratios(Cu:Cefepime) [(1:3)&(4:1)] ,Zn(II) and mixed metal [Fe(III),Ni(II)] cefepime complexes. Among the target compounds, Mn-cefepime complex showed the highest inhibitory activity 66.6% towards AChE with IC50 945μM. The Lineweaver–Burk plot of the inhibition of AChE by the investigated inhibitors indicates a pattern of inhibition of uncompetitive type , On the other hand, Zn-cefepime complex could be accounted as non-competitive inhibitors to AChE, where it caused decrease in Vmax– value and did not alter the Km Also, the inhibition of MAO-B by Cr(III), Cu(II), Mn(II) and mixed metals [Fe(III),Ni(II)] &[Fe(III),Cu(II)] cefepime complexes was uncompetitive type. Mn-cefepime complex showed the highest inhibitory activity 96.36% towards MAO-A, while mixed metal complexes [Fe(III),Ni(II)] &[Fe(III),Cu(II)] cefepime complexes gave the highest inhibitory activity 75.39% towards MAO-B . The Ki and IC50 values for metallo cefepime inhibitors were evaluated. Therefore, some of synthesized metallocefepime can be used for preventing neurodegenerative diseases such as Alzheimer΄s disease.