Abstract

SYNTHESIS, CHARACTERIZATION AND ENZYMETIC EVALUATION OF NOVEL BIS DERIVATIVES OF AZETIDINONE AND OXAZOLIDINONE DERIVED FROM ORTHOTOLIDINE

Shaima Ibraheem Chyad Al-khazraji*, Hala Mohammad G. Al-zahawi, Mustafa R. Albayati

ABSTRACT

In this work, a series of novel potential chemotherapeutic compounds of azetidinones and oxazolidinones have been synthesized utilizing ortho-Tolidine as a starting core. The synthesis route in this work can be summarized simply through the condensation of orthotolidine with different aldehydes in 1:2 molar ratio to furnish bisSchiff's bases (1-11). Some of These bis Schiff's bases have been treated with cloroacetylchloride and glycolic acid in 1:2 molar ratio to afford bisazetidinone derivatives (12-17) and bisOxazolidinone derivatives (18-20) respectively. All the prepared compounds were characterized spectroscopically by FT-IR spectroscopy and for some of the compounds by (1H-NMR and 13C-NMR) and almost them were matched the validity of the proposed structure. This study is designed to show the effect of sevene new prepared heterocyclic compounds on the activity of human AChE and equine serum BuChE using Ellman's method (using appropriate reference agents donepezil). All compounds showed strong inhibition ranging between (80.3 %-93.7%) at concentration up to 1x 10-1 M.it was found that the percentage of inhibition is increased with the increase of concentration of inhibitors. Especially, compound 14 showed the best AChE and BuChE inhibitory activity of all the synthesized derivatives, with an IC50 value of 0.2 mM and 3.7 mM.. Lineweaver-Burk plots were used to determine the type of inhibition, all studied compounds behaved as non-competitive inhibitors.

Keywords: B-Lactam, azetidinone, oxazolidine, Schiff base.