Synthesis, carbonic anhydrase I and II isoenzymes inhibition properties, and antibacterial activities of novel tetralone-based 1,4-benzothiazepine derivatives.

Abstract

Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92nM against hCA I and 33.60nM against hCA II, respectively.