New Thiazole Derivatives: Carbonic Anhydrase I-II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

Abstract

Thiosemicarbazone derivative was obtained by the addition of thiosemicarbazide to 5-nitro-thiophene-2-carbaldehyde. The addition-cyclization of the 2-bromoacetophenone derivative to thiosemicarbazone derivative gave the new thiazole derivatives (2 a-k). Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), antioxidant, and human carbonic anhydrase (hCA) I and II isoform inhibitory activities of the thiazole derivatives 2 a-k were investigated. The effects of thiazole derivatives on carbonic anhydrase I and II (hCA I-II) isoenzymes were examined in vitro using the esterase method. IC50 values for enzyme inhibition were found to be 2.661-22.712 mu M for hCA I and 5.372-26.813 mu M for hCA II. All derivatives reduced the activities of carbonic anhydrase I and II isoenzymes and were new potential inhibitor molecule candidates. These compounds were found to have minimal effects on AChE and BChE. The antioxidant properties of the target compounds were determined using DPPH and ferric ion-chelating assays. In particular, compounds 2 k and 2 h had the highest antioxidant effect in the series with IC50 values of 30.11 +/- 0.008 mu M and 30.21 +/- 0.006 mu M, respectively. ADMET properties of the compounds found to be effective were evaluated and their interactions with the enzyme were determined by molecular docking.