Synthesis and docking calculations of tetrafluoronaphthalene derivatives and their inhibition profiles against some metabolic enzymes
Date
5 FebruaryMetadata
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Musa Erdoğan1 | Parham Taslimi2 | Burak Tuzun3 1- Department of Food Engineering, Faculty of Engineering and Architecture, Kafkas University, Kars, Turkey 2- Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey 3- Chemistry Department, Science Faculty, Sivas Cumhuriyet University, Sivas, TurkeyAbstract
Syntheses of tetrahydroepoxy, O‐allylic, O‐prenylic, and O‐propargylic tetrafluoronaphthalene
derivatives, starting from 1‐bromo‐2,3,4,5,6‐pentafluorobenzene,
are reported here for the first time. The O‐substituted tetrafluoronaphthalene derivatives
were designed and also synthesized via a one‐pot nucleophilic substitution
reaction in excellent yields, whereas the tetrafluorotetrahydroepoxynaphthalene
derivate was synthesized via a reduction reaction in excellent yield. The chemical
structures of all the synthesized molecules were characterized by nuclear magnetic
resonance, infrared spectroscopy, and high‐resolution mass spectrometry techniques.
In this study, a series of novel tetrafluoronaphthalene derivatives (2, 2a, 4–6) was
tested toward several enzymes including α‐glucosidase, acetylcholinesterase (AChE),
and human carbonic anhydrase I and II (hCA I/II). The tetrafluoronaphthalene derivatives
2, 2a, and 4–6 showed IC50 and Ki values in the range of 0.83–1.27 and
0.71–1.09 nM against hCA I, 1.26–1.85 and 1.45–5.31 nM against hCA II,
39.02–56.01 and 20.53–56.76 nM against AChE, and 15.27–34.12 and
22.58–30.45 nM against α‐glucosidase, respectively. Molecular docking calculations
were made to determine the biological activity values of the tetrafluoronaphthalene
derivatives against the enzymes. After the calculations, ADME/T analysis was performed
to examine the effects on human metabolism. Finally, these compounds had
antidiabetic and anticholinesterase potentials.