The synthesis, carbonic anhydrase and acetylcholinesterase inhibition effects of sulfonyl chloride moiety containing oxazolidinones using an intramolecular aza-Michael addition

Abstract

Oxazolidinones are used as various potent antibiotics, in organisms it acts as a protein synthesis inhibitor, focusing on an initial stage that encompasses the tRNA binding process. Novel intramolecular aza-Michael reactions devoid of metal catalysts have been introduced in an oxazolidone synthesis pathway, different from α,β-unsaturated ketones. Oxazolidinone derivatives were tested against acetylcholinesterase (AChE), carbonic anhydrase I and II (hCA I and hCA II) enzymes. All the synthesized compounds had potent inhibition effects with Ki values in the range of 13.57 ± 0.98 − 53.60 ± 6.81 µM against hCA I and 9.96 ± 1.02 − 46.35 ± 3.83 µM against hCA II in comparison to the acetazolamide (AZA) (Ki = 50.46 ± 6.17 µM for hCA I) and for hCA II (Ki = 41.31 ± 5.05 µM). Also, most of the compounds demonstrated potent inhibition ability towards AChE enzyme with Ki values 78.67–231.75 nM and compared to tacrine (TAC) as standard clinical inhibitor (Ki = 142.48 nM). Furthermore, ADMET analysis and molecular docking were calculated using the AChE, hCA I and hCA II enzyme proteins to correlate the data with the experimental data. In this work, recent applications of a stereoselective aza-Michael reaction as an efficient tool for of nitrogen-containing heterocyclic scaffolds and their useful to pharmacology analogs are reviewed and summarized. Communicated by Ramaswamy H. Sarma