The human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibition effects of trimethoxyindane derivatives

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) had six genetically distinct families described to date in various organisms. There are 16 known CA isoforms in humans. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. Acetylcholine esterase (AChE. EC 3.1.1.7) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine relaying the signal from the nerve. In this study, some trimethoxyindane derivatives were investigated as inhibitors against the cytosolic hCA I and II isoenzymes, and AChE enzyme. Both hCA isozymes were inhibited by trimethoxyindane derivatives in the low nanomolar range. These compounds were good hCA I inhibitors (Kis in the range of 1.66-4.14 nM) and hCA II inhibitors (Kis of 1.37-3.12 nM) and perfect AChE inhibitors (Kis in the range of 1.87-7.53 nM) compared to acetazolamide as CA inhibitor (Ki: 6.76 nM for hCA I and Ki: 5.85 nM for hCA II) and Tacrine as AChE inhibitor (Ki: 7.64 nM).

The effects of some bromophenols on human carbonic anhydrase isoenzymes

“…The clinical usage of CAIs has been established as antiglaucoma agents, diuretics and anti-epileptic. CAIs were also used in the treatment of mountain sickness, osteoporosis, gastric and duodenal ulcers and neurological disorders [60][61][62] . Both physiologically relevant hCA I, and II isoforms were included in our study.…”

“…The bromophenol 11, which had two methoxy (-OH) and a bromine (-Br) groups, was the best hCA II inhibitor (K i : 2.01 ± 0.52 nM). Phenolic compounds have a lot of nutritional and pharmacological properties including anti-oxidant properties [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] and enzymes inhibition [82][83][84][85][86] . However, all bromophenol derivatives (1-12) have shown similar hCA II inhibition properties.…”

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

“…13 Synthesis of allyl 4-(2-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (6)…”

“…Indeed, bicarbonate is a substrate for several carboxylation enzymes involved in biosynthetic pathways such as biosynthesis of urea, glucose, fatty acids and possibly nucleotides [7][8][9][10] . The reaction not only provides a means to control the physiological pH values, but also supplies HCO 3 À ions for various physiological processes or metabolic, biosynthetic pathways, as those mentioned above [11][12][13][14] . So far, six unrelated genetic CA families have been discovered, namely, the a-, b-, g-, d-, z-and Z-CAs.…”

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

“…In mammals, CA II, which generally exists in red blood cells in lower concentrations, has approximately 10 times higher activity compare with CA I [99][100][101][102] . Cytosolic hCA I isoenzyme is ubiquitously expressed in body, and available in high concentrations in blood and gastrointestinal tract.…”