Browsing by Author "Erdogan, M."

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Novel asymmetric biscarbothioamides as Alzheimer's disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies
(2024.01.01) Muglu, H.; Yakan, H.; Erdogan, M.; Topal, F.; Topal, M.; Turkes, C.; Beydemir, S.
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. Investigating innovative frameworks for addressing Alzheimer's disease is a challenging goal. In this specific scenario, a selection of asymmetric biscarbothioamide derivatives (3a-l) with different substitutions has been carefully formulated and successfully synthesized.
Synthesis, theoretical, in silico and in vitro biological evaluation studies of new thiosemicarbazones as acetylcholinesterase and carbonic anhydrases inhibitors.
(2023-09-28) Erdogan, M.; Çavus, S.; Muğlu, H.; Yakan, H.; Türkeş, C.; Demir, Yeliz; Beydemir, Şükrü
Eleven new thiosemicarbazone derivatives (1-11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted-thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one-step easy synthesis and an eco-friendly process, the designed compounds were synthesized with yields of up to 95% from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxyl groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT-IR, 1H NMR, and 13C NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6-311++G(2d,2p) level of theory, and the experimental findings were supported. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 23.54±4.34 to 185.90±26.16 nM, 103.90±23.49 to 325.90 ±77.99 nM, and 86.15±18.58 to 287.70±43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme-ligand complex's interaction.
Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors
(2023.01.01) Erdogan, M.; Cavus, M.S.; Muglu, H.; Yakan, H.; Türkes, C.; Demir, Y.; Beydemir, S.
Eleven new thiosemicarbazone derivatives (1-11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted-thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one-step easy synthesis and an eco-friendly process, the designed compounds were synthesized with yields of up to 95 % from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxy groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT-IR, H-1-NMR, and C-13-NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6-311++G(2d,2p) level of theory, and the experimental findings were supported. The effects of some global reactivity parameters and nucleophilic-electrophilic attack abilities of the compounds on the enzyme inhibition properties were also investigated. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (K-I values are in the range of 23.54 +/- 4.34 to 185.90 +/- 26.16 nM, 103.90 +/- 23.49 to 325.90 +/- 77.99 nM, and 86.15 +/- 18.58 to 287.70 +/- 43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme-ligand complex's interaction.