The synthesis of some beta-lactams and investigation of their metal-chelating activity, carbonic anhydrase and acetylcholinesterase inhibition profiles

Abstract

beta-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. Synthesis of beta-lactam analogs, which are containing dichloride atoms and N-methyl, N-aromatic rings, was achieved by Schiff bases and dichloroketene compounds. All the synthesized imines and beta-lactam analogs were tested against two physiologically relevant carbonic anhydrase isozymes (hCA I and II) and acetylcholinesterase (AChE). They demponstrated effective inhibitory profiles with K-i values in ranging of 3.22-11.18 nM against hCA I, 3.74-10.41 nM against hCA II, and 0.50-1.57 nM against AChE. On the other hand, acetazolamide and dorzolamide clinically used as CA inhibitors, showed K-i value of 170.34 and 129.26nM against hCA I, and 115.43 and 135.67 nM against hCA II, respectively. Also, tacrine used as standard AChE inhibitor showed Ki value of 5.70 nM against AChE.