Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

Abstract

A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209-0.291 nM. On the other hand, tacrine, which is used in the treatment of Alzheimer's disease possessed lower inhibition effect (K i : 0.398 nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (K i ) in the range of 4.49-5.61 nM for hCA I, and 4.94-7.66 nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated K i values of 281.33 nM for hCA I and 9.07 nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels.

Novel NHC Precursors: Synthesis, Characterization, and Carbonic Anhydrase and Acetylcholinesterase Inhibitory Properties

“…Moreover, it was reported that AChEIs had healing effect for AD treatment on cognition and on behavioral symptoms by clinical studies . Furthermore, the designing of new AChEIs that interact with the peripheral anionic site is extremely important for the AD treatment . The inhibition effects of the newly synthesized NHC precursors on AChE are shown in Table .…”

Inhibition properties of some flavonoids on carbonic anhydrase I and II isoenzymes purified from human erythrocytes

“…Carbonic anhydrase isoenzymes play a key role in many pathophysiological events including CO 2 /HCO 3 − transport and balance, biosynthesis reactions involving gluconeogenesis, urea synthesis, lipogenesis, respiration, calcification, tumorigenicity, electrolyte release in different tissues and organs, and bone resorption . CAs can be inhibited in the range of micromolar to nanomolar by sulfonamide and its derivatives . AZA is frequently used in the treatment of diseases such as glaucoma, epilepsy, altitude sickness .…”

Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities

“…Elder persons suffering from Alzheimer's disease (AD) have a low ACh level in the hippocampus and cortex, which is the main cause of AD 17,41 . Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) are serine hydrolases that catalyze the hydrolysis of acetylcholine, thus regulating cholinergic neurotransmission [42][43][44] . It is well known that both enzymes are two major forms of cholinesterases in mammalian tissues.…”