The synthesis, carbonic anhydrase and acetylcholinesterase inhibition effects of sulfonyl chloride moiety containing oxazolidinones using an intramolecular aza-Michael addition
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...
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Published in | Journal of biomolecular structure & dynamics pp. 1 - 16 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
15.12.2023
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Subjects | |
Online Access | Get full text |
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Summary: | 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) (
= 50.46 ± 6.17 µM for hCA I) and for hCA II (
= 41.31 ± 5.05 µM). Also, most of the compounds demonstrated potent inhibition ability towards AChE enzyme with
values 78.67-231.75 nM and compared to tacrine (TAC) as standard clinical inhibitor (
= 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0739-1102 1538-0254 |
DOI: | 10.1080/07391102.2023.2291163 |