Microwave assisted synthesis of benzo-azacrown ethers and in vitro inhibition studies on hCA I–II

Abstract

In this study, macro-ringed benzo-aza-oxa-crown ethers were synthesized by a cyclization reaction between 2,2′-dithiodianiline and mono/di/tri/tetraethylene glycol dichloride/dibromide with Cs2CO3 as a catalyst under nitrogen atmosphere by the SN2 mechanism using the microwave synthesis method, which is one of the green chemistry methods. Structural characterizations of the original 2,2′-dithiodibenzo crown ether derivatives were confirmed with melting point, FT-IR, 1H NMR, 13C NMR, LC-MS/MS, elemental analysis, UV and fluorescence spectroscopy methods. In addition, the inhibition effects of these synthesized four crown ethers on human erythrocyte carbonic anhydrase (hCA I–II) isoenzyme activities were investigated. The synthesized compounds include aromatic benzene rings, nitrogen, sulfur, and oxygen donor atoms. The effects of aromaticity, S,S′-disulfide bond, nitrogen and oxygen donor atoms on the activity of carbonic anhydrase isoenzyme have been studied. (1,8,11,18)-Tetraaza[2,3-6,7-12,13-16,17]tetrabenzo-(4,5,14,15)-tetrathiocycloeicosane showed the highest inhibition effect on hCA I (Ki = 0.353±0.154 µM) and hCA II (Ki = 1.588±0.998 µM) enzyme.