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A series of some naphthol derivatives 4a-f, 5a,f, 6a, and 7a,b (six novel ones: 4c,d, 5a, 6a, 7a,b) bearing F, Cl, Br, OMe, and dioxole substituents at different positions of the aromatic rings was designed, synthesized, and characterized. The naphthol derivatives were synthesized in three steps, namely the addition reaction of furan via Diels-Alder cycloaddition reaction, copper(II) trifluoromethanesulfonate (Cu(OTf) 2 )-catalyzed aromatization reaction, and the bromination reaction, respectively. The structures of the newly obtained compounds (4c,d, 5a, 6a, 7a,b) were characterized by spectroscopic techniques. In addition, some biological activity studies were investigated under in vitro conditions. Inhibition studies of these compounds were performed on human carbonic anhydrase (hCA) I and II isoenzymes purified from human erythrocytes as a biological evaluation. Moreover, their potential antioxidant and antiradical activities were studied by analytical methods like ABTS •+ and DPPH• scavenging, and it was determined that some molecules showed good activity. Also, inhibition of acetylcholinesterase (AChE), which is a marker of many degenerative neurological diseases, was tested and the results were discussed. Excellent enzyme inhibition results were recorded for most of the molecules. These 1-naphthol derivatives were found as effective inhibitors for hCA I, hCA II, and AChE with K i values ranging from 0.034 ± 0.54 to 0.724 ± 0.18 µM for hCA I, 0.172 ± 0.02 to 0.562 ± 0.21 µM for hCA II, and 0.096 ± 0.01 to 0.177 ± 0.02 µM for AChE., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

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 IC 50 and K i 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., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Exploring novel frameworks for treating Alzheimer's disease is an ambitious objective. In this particular context, a range of asymmetric biscarbothioamide derivatives (3a–l) with varying substitutions have been meticulously designed and effectively synthesized. The newly synthesized compounds have all been definitively characterized using established spectroscopic techniques such as 1H-NMR, 13C-NMR, FT-IR, and elemental analysis. In vitro, all the derivatives (3a–l) were evaluated to assess their inhibitory potential against cholinesterase enzymes (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE). The outcomes demonstrated that these derivatives were potent and exhibited selectivity in inhibiting AChE, except for compounds 3b and 3e, which specifically inhibited BChE, showcasing varying degrees of KI values. Significantly, compounds 3j (KIs of 11.91 ± 2.25 nM for AChE and 77.76 ± 8.02 nM for BChE) and 3h (KIs of 14.73 ± 2.30 nM for AChE and 59.54 ± 6.20 nM for BChE) emerged as the most potent dual inhibitors of AChE and BChE within the series, respectively, with KI constants even lower than those of the standard drug tacrine (KIs of 68.70 ± 5.39 nM for AChE and 111.60 ± 10.52 nM for BChE). Furthermore, their potential scavenging activity against DPPH and ABTS radicals was evaluated. To further validate the experimental findings, molecular docking studies were performed in silico to ascertain the binding modes of these compounds with the active pockets of AChE and BChE enzymes. [ABSTRACT FROM AUTHOR]