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 S(N)2 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, H-1 NMR, C-13 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 (K-i = 0.353 +/- 0.154 mu M) and hCA II (K-i = 1.588 +/- 0.998 mu M) enzyme.