Carbonic anhydrase inhibitors: 2-Substituted-1,3,4-thiadiazole-5-sulfamides act as powerful and selective inhibitors of the mitochondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrases I, II and IV

Heterocyclic compounds as carbonic anhydrase inhibitor

“…The new compounds showed weak inhibitory activity against hCA I (K I s of 102 nM-7.42 μM), hCA II (K I s of 0.54-7.42 μM) and hCA IV (K I s of 4.32-10.05 μM) but were low-nanomolar inhibitors of hCA VA and hCA VB, with inhibition constants in the range of 4.2-32 nM and 1.3-74 nM, respectively 19 . As extension of their former work C. Temperini et al 20 reported interaction of 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide [1] with the 12 catalytically active mammalian carbonic anhydrase isozymes, CA I-XIV.…”

“…Brzozowski et al 29 synthesized a series of novel 4-substituted-3-pyridinesulfonamides [14][15][16][17][18][19][20][21][22] and [23a-c] and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase that is, the cytosolic, ubiquitous isozymes CA I and II, and transmembrane isozymes CA IX, XII (cancer-associated) and XIV. The newly synthesized compounds showed inhibition constants in the range of 0.078-11.7 μM.…”

“…The classical recognition motif for small molecules to bind the active site of CA is an aromatic sulfonamide moiety (ArSO 2 NH 2 ). The deprotonated sulfonamide (ArSO 2 NH − ) coordinates to the CA active site Zn 2+ , and so inhibits the binding of the endogenous substrates (CO 2 and H 2 O), thereby reducing the catalytic ability of the enzyme 18,19 .…”

Microwave-Assisted One-Step Synthesis of 2,5-Disubstituted-1,3,4-Oxadiazoles Using 1,4- Bis(triphenylphosphonium)-2-Butene Peroxodisulfate

“…They exhibit, for example, antimicrobial, 6 antimycobacterial, 7 anticancer, [8][9] antiinflammatory, 10 carbonic anhydrase inhibiting effect, 11 antianxiety, antidepressant. 12 Several methods have been reported in the literature for the synthesis of 1,3,4-oxadiazoles.…”

Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

“…Heterocyclic sulfonamides have been found to be carbonic anhydrase inhibitors (Surpuran et al, 1998;Di Fiore et al, 2010;Smaine et al, 2008) and antibacterial (Gadad et al, 2000) and anticancer, antiinflammatory and analgesic (Sondhi et al, 2000) agents. Furthermore, the piperazine core has displayed a wide spectrum of pharmacological activities and is part of a number of drugs that are preclinical and clinical candidates (Welsch, Snyder, Stockwell, 2010;Hussain et al, 2016).…”