9,10‐Dibromo‐N‐aryl‐9,10‐dihydro‐9,10‐[3,4]epipyrroloanthracene‐12,14‐diones: Synthesis and Investigation of Their Effects on Carbonic Anhydrase Isozymes I, II, IX, and XII

Abstract

N-substituted maleimides were synthesized from maleic anhydride and primary amines. 1,4-Dibromo-dibenzo[e,h]bicyclo-[2,2,2]octane-2,3-dicarboximide derivatives (4a-f) were prepared by the [4+2] cycloaddition reaction of dibromoanthracenes with the N-substituted maleimide derivatives. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the new derivatives were assayed against the human (h) isozymes hCA I, II, IX, and XII. All tested bicyclo dicarboximide derivatives exhibited excellent inhibitory effects in the nanomolar range, with Ki values in the range of 117.73-232.87 nM against hCA I and of 69.74-111.51 nM against hCA II, whereas they were low micromolar inhibitors against hCA IX and XII.

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

“…Affinity chromatography is the most commonly used method for the purification of proteins and biomolecules due to its process simplicity, efficiency, specificity, and yield . Therefore, we purified the hCA I and II isozymes by using Sepharose‐4B‐L‐tyrosine‐sulphanilamide affinity column chromatography.…”

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

“…Then the reaction was initiated by the addition of 50 μL of AChI. The hydrolysis of AChI was recorded spectrophotometrically by the formation of 5-thio-2-nitrobenzoate anion as the result of the reaction of DTNB with thiocholine at a wavelength of 412 nm [77]. The IC 50 values were determined by spectrophotometric measurement of the effect of increasing test compound (β-lactam derivatives 2a – k ) concentrations on AChE activity.…”

Evaluation of acetylcholinesterase and carbonic anhydrase inhibition profiles of 1,2,3,4,6-pentasubstituted-4-hydroxy-cyclohexanes

“…CA inhibitors are widely studied recently due to their significant applications in the treatment and prevention of an extensive number of diseases . These two cytosolic isoenzymes are the predominant ones between the 16 CAs recorded to date in diverse tissues/cell in vertebrates . For instance, CA II is used as an excellent therapy of glaucoma and also plays a significant role in bicarbonate production in the eye .…”