Exploring the multi-target enzyme inhibition potential of new sulfonamido-thiazoline derivatives; synthesis and computational studies

[Display omitted] A small library of ten new Nimesulide-iminothiazolines conjugates was synthesized by the reduction of nitro group of Nimesulide followed by conversion into variously substituted acyl thioureas. Heterocyclization of the latter with phenacyl bromide afforded the products (7a-j) in good to excellent yields and high purity. The newly synthezied (7a-j) were screend for inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase I (hCA I) and carbonic anhydrase II (hCA II). Most of the synthesized molecules were more effective than standard inhibitors tacrine, and acetazolamide against AchE, BchE and against CA I and CA II respectively. Compounds 7 h, 7f, 7d and 7i were the most potent compounds against hCA I&II. Whilst compounds 7a, 7d and 7f showed highest inhibition against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) when compared with standard inhibitor Tacrine. In silico studies were also performed to find the type of interactions. Molecular docking was accomplished to explore the putative binding mode of interactions of selective inhibitors. Finally, the ADMET analysis of the molecules was also performed.