Microwave assisted synthesis of novel acridine–acetazolamide conjugates and investigation of their inhibition effects on human carbonic anhydrase isoforms hCA I, II, IV and VII

Bioorganic & Medicinal Chemistry
2016.0

Abstract

4-Amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide was condensed with cyclic-1,3-diketones (dimedone and cyclohexane-1,3-dione) and aromatic aldehydes under microwave irradiation, leading to a series of acridine-acetazolamide conjugates. The new compounds were investigated as inhibitors of carbonic anhydrases (CA, EC 4.2.1.1), and more precisely cytosolic isoforms hCA I, II, VII and membrane-bound one hCA IV. All investigated isoforms were inhibited in low micromolar and nanomolar range by the new compounds. hCA IV and VII were inhibited with KIs in the range of 29.7-708.8nM (hCA IV), and of 1.3-90.7nM (hCA VII). For hCA I and II the KIs were in the range of 6.7-335.2nM (hCA I) and of 0.5-55.4nM (hCA II). The structure-activity relationships (SAR) for the inhibition of these isoforms with the acridine-acetazolamide conjugates reported here were delineated.

DOI： 10.1016/j.bmc.2016.05.064

Knowledge Graph

Similar Paper

Microwave assisted synthesis of novel acridine–acetazolamide conjugates and investigation of their inhibition effects on human carbonic anhydrase isoforms hCA I, II, IV and VII
Bioorganic & Medicinal Chemistry 2016.0
Synthesis of novel acridine and bis acridine sulfonamides with effective inhibitory activity against the cytosolic carbonic anhydrase isoforms II and VII
Bioorganic & Medicinal Chemistry 2013.0
Microwave assisted synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine, xanthene and chromene skeletons as inhibitors of the carbonic anhydrases isoforms I, II, IV and VII
Bioorganic & Medicinal Chemistry Letters 2017.0
Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties
Bioorganic & Medicinal Chemistry 2017.0
Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity against the carbonic anhydrase isoforms I, II, IX and XII
Bioorganic & Medicinal Chemistry 2015.0
Pyridazinone substituted benzenesulfonamides as potent carbonic anhydrase inhibitors
Bioorganic & Medicinal Chemistry Letters 2016.0
Carbonic anhydrase inhibitors: Synthesis and inhibition of the cytosolic mammalian carbonic anhydrase isoforms I, II and VII with benzene sulfonamides incorporating 4,5,6,7-tetrachlorophthalimide moiety
Bioorganic & Medicinal Chemistry 2013.0
Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: Kinetic and X-ray crystallographic studies
Bioorganic & Medicinal Chemistry Letters 2008.0
Effects of new 5-amino-1,3,4-thiadiazole-2-sulfonamide derivatives on human carbonic anhydrase isozymes
Bioorganic & Medicinal Chemistry 2009.0
Benzenesulfonamide bearing imidazothiadiazole and thiazolotriazole scaffolds as potent tumor associated human carbonic anhydrase IX and XII inhibitors
Bioorganic & Medicinal Chemistry 2017.0