Modification of Acetazolamide Synthesis: New Derivatives and Investigation of Their Biological Properties

Abstract

Abstract Acetazolamide 1 is a carbonic anhydrase inhibitor used in the medical treatment of glaucoma, epileptic seizure, idiopathic intracranial hypertension, altitude sickness, etc. The synthesis of `acetazolamide from the corresponding thiol derivative 2 requires oxidation and converting it to the sulfonyl chloride intermediate 3. This research tries to improve the safety, green conditions and efficiency of the oxidation method. For this purpose, chlorine gas was replaced with sodium hypochlorite (commercial bleach). This procedure led to the synthesis of several new products 1a-f with high purity. The synthesized key sulfonyl chloride 3 in the reaction with various amines, hydrazones, and bis-amines led to several new sulfonamide derivatives. The antibacterial activity (AA) and antioxidant activity (AO) of the newly synthesized compounds was investigated. The AA effect of bis-products (4a and 4b) is significantly increased compared to the corresponding mono-product (1a). In addition, the synthesized hydrazine-based products (10a-10 g) showed a very good effect on all Gram-positive and Gram-negative bacteria compared to other products, especially (11 g), compared to ciprofloxacin and tetracycline. Compounds 11c, 11a, 11b, 11e, and 1d showed good AO compared to ascorbic acid.