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

The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α‐glycosidase enzymes: An antidiabetic, anticholinergic, and antiepileptic study

“…IC 50 values of phenolic molecules and standard (tacrine) compound exhibited the following order: hesperidin (0.85 nM) < naringin (29.10 nM) < chrysin (31.63 nM) < carvacrol (82.81 nM) < zingerone (94.98 nM) < AZA (276.22 nM) (Figure ). (iv)BChE involves three enzymatic acts in its structure like its sister enzyme AChE: peptidase (or protease), esterase, and aryl acylamidase . For BChE enzyme, the natural phenolic compounds had K i values in the range of 1.25 ± 0.22–32.08 ± 2.68 and IC 50 values in the range of 3.45–79.11 nM (Table ).…”

Inhibitory effects of some drugs on carbonic anhydrase enzyme purified from Kangal Akkaraman sheep in Sivas, Turkey

“…Recently, interactions of ceftriaxone, morphine, imipenem, diprophylline, acyclovir, proxyphylline, aminophylline, caffeine, midazolam, and diazepam with the CA human isoforms of I and II were investigated and provided the possibility to design isoform‐specific CAIs . While the inhibition profiles of drugs on different CA isoforms are in ranges starting from millimolar to submicromolar levels, it is reasonable to suggest the furthering of previous studies with commonly used drugs such as this study.…”

Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base

“…Recently, the interactions of AChE and BChE with cyclic thioureas, hetaryl sulfonamides, Mannich bases, ureas derived from phenethylamines, tetrahydropyrimidines, diaryl ethers, β‐lactams, benzenesulfonamides, and tetrahydropyrimidine‐5‐carboxylates as well as the interactions for both CA isoenzymes with caffeic acid phenethyl ester, polyphenols and phenolic acids, benzotropones, bromophenols, dopaminergic compounds, sulfamides, sulfonamides, acylsulfonamides, benzenesulfonamides, 1,3,5‐trisubstituted‐pyrazolines,, tetralone‐based 1,4‐benzothiazepine derivatives, novel eugenol derivatives, some natural sulfonamide derivatives, and novel (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(3‐aryl)acryloyl) phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione derivatives benzylsulfamides have been studied.…”