Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights

Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors

“…The yield of acetamide 15 was 6.2 g (99%), white crystals, mp 185-187 °C. 1 (16). The mixture of concentrated HNO 3 (7.0 mL, 0.17 mol) and concentrated H 2 SO 4 (10.0 mL, 0.18 mol) was cooled to 0 °C.…”

“…1 ). 16 One well-known example of a CA inhibitor is acetazolamide (AAZ, shown as 1 in Fig. 1 ), which has been used in clinical practice for over 40 years and can suppress tumor cell proliferation through CA inhibition.…”

Novel 2,4-Dichloro-5-sulfamoylbenzoic Acid Oxime Esters: First Studies as Potential Human Carbonic Anhydrase Inhibitors

“…In such a context, the validation of new druggable targets is highly beneficial for the sustainability of the currently used therapeutical protocols. Among the most promising experimental targets, a place of honor is held by the metalloenzymes carbonic anhydrases (CAs; EC 4.2.1.1), which are proven to be crucial for fundamental cancer-related cellular processes. , CAs are involved in regulating pH levels, transporting ions, and maintaining the CO 2 homeostasis. The α-class of CAs expressed in humans (hCAs) accounts for 16 distinct isoforms and, among them, the transmembrane isoforms IX and XII are directly involved in carcinogenesis, whereas the cytosolic isoforms hCA I and hCA II are widely expressed in organs, such as eyes, erythrocytes, osteoclasts, the gastrointestinal system, and kidney cells, and are cooperative with the tumor-associated isoenzymes. − …”

New Structural Features of Isatin Dihydrothiazole Hybrids for Selective Carbonic Anhydrase Inhibitors

“…In the human body, members of the carbonic anhydrase enzyme family are involved in pH regulation and other physiological functions. , These proteins are ubiquitous metalloenzymes that contain a zinc ion in the active site, where the reversible hydration of carbon dioxide into bicarbonate ions and protons is catalyzed. , In mammals more than 16 different isoforms of hCAs are found, differing in their sequence, tissue localization, expression, and activity. − Since these enzymes are involved in several physiological and pathological metabolic pathways, their role as drug targets has been investigated. ,, In particular, isoforms IX and XII play key roles in proliferation, cell differentiation, and pH regulation. Furthermore, isoform IX is overexpressed in different types of tumors. , For this reason, hCA IX and XII inhibitors have been deeply explored as anticancer agents. ,− Both represent attractive targets for selective inhibition compared with other hCA isoforms due to their relatively limited expression in normal tissues. These two isoforms are transmembrane and not cytosolic.…”