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

Abstract

b-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contain a b-lactam ring in their molecular structures. Synthesis of b-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 b-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 129.26 nM against hCA I, and 115.43 and 135.67 nM against hCA II, respectively. Also, tacrine used as standard AChE inhibitor showed K i value of 5.70 nM against AChE.

Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis, characterization, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibitory properties

“…[54] In this study, we obtained the effects of novel amides of 1,1-bis-(carboxymethylthio)-1arylethanes derivatives (1-11) against hCA I, hCA II, AChE, and BChE enzymes. [55] In addition, hCA II is the most TA B L E 1 The enzyme inhibition results of novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) extensively studied and characterized of the hCA isoforms. hCA II is often associated with several diseases such as glaucoma, osteoporosis, and renal tubular acidosis.…”

“…[25][26][27][28][29] In this study, we have performed the synthesis of well-defined novel amide of 1,1-bis-(carboxymethylthio)-1-arylethanes derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). [25][26][27][28][29] In this study, we have performed the synthesis of well-defined novel amide of 1,1-bis-(carboxymethylthio)-1-arylethanes derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Discovery of Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors: 2-Aminoindan β-Lactam Derivatives

“…It is well known that β-lactams had inhibition properties on hCA I, and II isoenzymes and are used in therapies [52,53]. The inhibition effects of newly synthesized compounds 2a – k were determined for the first time against hCA I, and II.…”

“…Also, β-lactam derivative 2g shown the most powerful CA I inhibition effect with a K i value of 0.35 ± 0.105 nM. On the other hand, we found that acetazolamide (AZA), which is used as a clinical CA inhibitor in the treatment of glaucoma, cystinuria, epilepsy, altitude sickness, periodic paralysis, dural ectasia, idiopathic intracranial hypertension, and central sleep apnoea [52], has a K i value of 170.34 ± 2.48 nM (Table 2). The results clearly show that all β-lactam derivatives 2a – k demonstrate more effective hCA inhibitory activity than that of AZA.…”

Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions

“…Six distinct genetic CA families, the a-, b-, g-, d-, z-and Z-CAs, are known to date, constituting an interesting example of convergent evolution at the molecular level [30][31][32] . Also, to date, 16 different CA isoenzymes are described in various organisms 33,34 .…”