Salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole, a structural and analog of acetazolamide, show interesting carbonic anhydrase inhibitory properties, diuretic, and anticonvulsant action

Abstract

Three salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole (Hats) were prepared and characterized by physico-chemical methods. The p-toluensulfonate, the methylsulfonate, and the chlorhydrate monohydrate salts of Hats were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) and as anticonvulsants and diuretics, since many CAIs are clinically used as pharmacological agents. The three Hats salts exhibited diuretic and anticonvulsant activities with little neurotoxicity. The human (h) isoforms hCA I, II, IV, VII, IX, and XII were inhibited in their micromolar range by these salts, whereas pathogenic beta and gamma CAs showed similar, weak inhibitory profiles.

Sebacoyl Isothiocyanate in the Synthesis of Bis (1,3,4-Thiadiazole, 1,3,4-Thiadiazolo[3,2-a]Pyridine, 4-Thiazolidinone, Chromenes, and Naphtho[1,2-b][1,4]Oxazine) Derivatives

“…Among the wide range of heterocycles studied to develop pharmaceutically significant molecules, 1,3,4-thiadiazole has played a significant role in medicinal chemistry. Moreover, 1,3,4-thiadiazole nucleus has fascinated significance in medicinal chemistry, displaying pharmacological properties such as, antimicrobial [8][9][10] , anti-inflammatory 11 , antitumor 12,13 , anticonvulsant 14,15 , antioxidant 16 , antifungal 17 , antitubercular 18 , and antidepressant activities 19 .…”

Synthesis and diuretic activity of novel 5-amino-1,3,4-thiadiazole-2-thiol derivatives

“…The shift of pH value to 8.0-8.5 (low alkali) was observed in urinalysis groups treated with 2a, 2c, 2e compared to the intact animals where the pH was 7.1. Such pH shift is a typical pharmacokinetic feature for 1.3.4-thiadiazol-bearing diuretics [21][22][23]. No negative changes such as appearance of glucose, protein, nitrite, occult blood in urine, or increasing specific gravity value were observed under the treatment with 2a, 2c, 2e.…”

“…The modified 1,3,4-thiadiazole nucleus is known as a scaffold for the design of potent derivatives with diuretic action [16][17][18][19]. The acetazolamide and methazolamide ( Fig.1) present widely used diuretic drugs with 1,3,4-thiazdiazole core belong to the carbonic anhydrase inhibitors (CAIs) [20][21][22][23].…”

1,3,4-Thiadiazole Scaffold: As Anti-Epileptic Agents

“…tosylate protein. It concluded that 5-amino-2-sulfonamide thiadiazole showed 72%-79% protection at 90 mg/kg against both the standard used when compared with its synthesized salts with no neurotoxicity; good binding affinity toward the selected protein by inhibiting carbonic anhydrase was also observed and was found effective against mild convulsions (Diaz et al, 2016).…”