2019
DOI: 10.1080/14756366.2018.1543292
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(Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators

Abstract: Using histamine as lead molecule, a library of (hetero)aryl substituted thiazol-2,4-yl derivatives incorporating pyridine as proton shuttling moiety were obtained and investigated as activators of human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, VII and XIV. Some derivatives displayed good activating and selectivity profiles. This study provides an interesting opportunity to study the thiazole scaffold for the design of CA activators (CAAs), possibly acting on the central nervous system and targeting … Show more

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Cited by 8 publications
(18 citation statements)
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“…Working at substrate concentrations considerably lower than K M ([S] << K M ), and considering that [A] f can be represented in the form of the total concentration of the enzyme ([E] t ) and activator ([A] t ), the obtained competitive steady-state equation for determining the activationconstant is given by Equation (5): v=v0×KA/false{KA+false(false[normalAfalse]t0.5false{false(false[normalAfalse]t+false[normalEfalse]t+KAfalse)false(false[normalAfalse]t+false[normalEfalse]t+KAfalse)24false[normalAfalse]t×false[normalEfalse]tfalse)1/2false}false} where v 0 represents the initial velocity of the enzyme-catalyzed reaction in the absence of an activator [43,44,45]. The equilibrium constants measured using this approach are in excellent agreement with those obtained from other methods, including native mass spectrometry and fluorescence spectroscopy [46].…”
Section: Methodsmentioning
confidence: 99%
“…Working at substrate concentrations considerably lower than K M ([S] << K M ), and considering that [A] f can be represented in the form of the total concentration of the enzyme ([E] t ) and activator ([A] t ), the obtained competitive steady-state equation for determining the activationconstant is given by Equation (5): v=v0×KA/false{KA+false(false[normalAfalse]t0.5false{false(false[normalAfalse]t+false[normalEfalse]t+KAfalse)false(false[normalAfalse]t+false[normalEfalse]t+KAfalse)24false[normalAfalse]t×false[normalEfalse]tfalse)1/2false}false} where v 0 represents the initial velocity of the enzyme-catalyzed reaction in the absence of an activator [43,44,45]. The equilibrium constants measured using this approach are in excellent agreement with those obtained from other methods, including native mass spectrometry and fluorescence spectroscopy [46].…”
Section: Methodsmentioning
confidence: 99%
“…where v 0 represents the initial velocity of the enzyme-catalyzed reaction in the absence of activator [34][35][36][37].…”
Section: Biological Assaysmentioning
confidence: 99%
“…Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes in all kingdoms 5–7 . They catalyze the reversible hydration of CO 2 with formation of bicarbonate and protons, converting thus efficiently two neutral molecules (CO 2 and H 2 O) in a weak base (bicarbonate) and a very strong acid (H + ions) 8–10 . For this reason, in most organisms investigated so far, from simple (such as bacteria and archaea) to complex ones (plants, animals etc.)…”
Section: Introductionmentioning
confidence: 99%
“…CA inhibitors (CAIs) belonging to many diverse chemotypes and possessing a wealth of inhibition mechanisms 5–7 are clinically used for the management of a variety of disorders, including edema, epilepsy, glaucoma, obesity, hypoxic tumors, neuropathic pain and arthritis 5–7 , 11–17 . On the other hand, CA activators (CAAs) started to be investigated in detail only in the last two decades, after the CA activation mechanism has been explained by one of our groups 8–10 .…”
Section: Introductionmentioning
confidence: 99%
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