Synthesis of new thiazole derivatives as inhibitors of acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase I, II enzymes

In this study, thiosemicarbazone derivative were obtained by the addition of thiosemicarbazide to the 5-nitro-thiophene-2-carbaldehyde. New thiazole derivatives (2a-2k) were synthesized by cyclization of 2-bromoacetophenone derivatives with thiosemicarbazone derivative. Acetylcholinesterase (AChE), butyrylcholinesteraseenzyme (BChE), antioxidant, and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 2a-2k were investigated. IC50 values for enzyme inhibition were found to be 2.661-22.712 µM for hCA I and 5.372-26.813 µM for hCA II. It was observed that all derivatives reduced the activities of carbonic anhydrase I and II isoenzymes and were new potential inhibitor molecule candidates. The compounds were found to have low effects against AChE and BChE enzymes. The antioxidant properties of the target compounds were determined by using DPPH and ferric ion chelating effect assays. Especially compounds 2k and 2h have the highest antioxidant effect in the series with IC50 values of 30.11 ± 0.008 μM and 30.21 ± 0.006 μM. ADMET properties of the compounds found to be effective were evaluated and their interactions with the enzyme were determined by molecular docking.