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Bioorg Med Chem. 2015 Jul 1;23(13):3592-602. doi: 10.1016/j.bmc.2015.04.019. Epub 2015 Apr 14.

Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: novel sulfamoylcarbamates and sulfamides derived from acetophenones.

Author information

1
Ağrı İbrahim Çeçen University, Central Researching Laboratory, Ağrı, Turkey; Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey.
2
Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey; Fetal Programming of Diseases Research Chair, Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
3
Department of Biophysics, School of Medicine, Bahçeşehir University, İstanbul, Turkey.
4
Università degli Studi di Firenze, Neurofarba dept., Via U Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy.
5
Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey. Electronic address: sgoksu@atauni.edu.tr.

Abstract

In this study, several novel sulfamides were synthesized and evaluated for their acetylcholine esterase (AChE) and human carbonic anhydrase I, and II isoenzymes (hCA I and II) inhibition profiles. Reductive amination of methoxyacetophenones was used for the synthesis of amines. Amines were converted to sulfamoylcarbamates with chlorosulfonyl isocyanate (CSI) in the presence of BnOH. Pd-C catalyzed hydrogenolysis of sulfamoylcarbamates afforded sulfamides. These novel compounds were good inhibitors of the cytosolic hCA I, and hCA II with Ki values in the range of 45.9±8.9-687.5±84.3 pM for hCA I, and 48.80±8.2-672.2±71.9pM for hCA II. The inhibitory effects of the synthesized novel compounds on AChE were also investigated. The Ki values of these compounds were in the range of 4.52±0.61-38.28±6.84pM for AChE. These results show that hCA I, II, and AChE were effectively inhibited by the novel sulfamoylcarbamates 17-21 and sulfamide derivatives 22-26. All investigated compounds were docked within the active sites of the corresponding enzymes revealing the reasons of the effective inhibitory activity.

KEYWORDS:

Acetylcholine esterase; Carbonic anhydrase; Enzyme inhibition; Hybrid molecules; Molecular docking; Sulfamide; Sulfamoylcarbamate

PMID:
25921269
DOI:
10.1016/j.bmc.2015.04.019
[Indexed for MEDLINE]

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