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Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors

N-(1-(4-Methoxyphenyl)-3-oxo-3-((4-(N-(substituted)sulfamoyl)phenyl)amino)prop-1-en-1-yl)benzamides 3a – g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by 1 H NMR, 13C NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. | Turkish Journal of Chemistry Turk J Chem 2020 44 1601-1609 http journals.tubitak.gov.tr chem TÜBİTAK Research Article doi 10.3906 kim-2007-37 Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors 1 1 2 2 Mehtap TUĞRAK Halise İnci GÜL Barış ANIL İlhami GÜLÇİN 1 Department of Pharmaceutical Chemistry Faculty of Pharmacy Atatürk University Erzurum Turkey 2 Department of Chemistry Faculty of Science Atatürk University Erzurum Turkey Received 17.07.2020 Accepted Published Online 08.09.2020 Final Version 16.12.2020 Abstract N- 1- 4-Methoxyphenyl -3-oxo-3- 4- N- substituted sulfamoyl phenyl amino prop-1-en-1-yl benzamides 3a g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase AChE and human carbonic anhydrase I and II hCA I and hCA II inhibitory potencies. Structure elucidation of the compounds was carried out by 1H NMR 13C NMR and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I hCA II and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 0.38 29.70 3.18 nM for hCA I and 10.68 0.98 37.16 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 1.65 34.02 5.90 nM. The most potent inhibitors 3g Ki 4.07 0.38 nM hCA I 3c Ki 10.68 0.98 nM hCA II and 3f Ki 8.91 1.65 nM AChE can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes. Key words Sulfonamide benzamide carbonic anhydrase acetylcholinesterase enzyme inhibition 1. Introduction Owing to significant bioactivities of benzamide pharmacophores this group of compounds has been used for designing novel and .