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

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 K i value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with K i value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed K i value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively.