Yazar "Sağlam, Mehmet F." seçeneğine göre listele

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    Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling
    (Elsevier B.V., 2024) Ceyhan, Sadık M.; Zengin, İrem Nur; Bingül, Murat; Şahin, Hasan; Boǧa, Mehmet; Sağlam, Mehmet F.; Kandemir, Hakan
    A new range of indolyl imine system 3d-l has been successfully prepared from 4,6-dimethoxy-2,3-diphenyl-indole-7-carbaldehyde 2a and 4,6-dimethoxy-3-aryl-indole-7-carbaldehyde 2b-c via Schiff base reaction. The structure of targeted compounds was confirmed by 1H and 13C NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction techniques. The indolyl imine derivatives were also subjected to in vitro antidiabetic activities employing ?-glucosidase and ?-amylase enzymes. In terms of antidiabetic investigation, the ?-glucosidase enzyme was found to be potential target due to the comparable inhibition concentrations with the standard acarbose and the compound 3e exhibited better potency than the standard. The anticholinesterase potency of the compounds was investigated towards the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The compounds displayed moderate efficiency against the BChE enzyme with the best inhibition concentration of 30.48 ?M by the compound 3h. The antioxidant properties of final compounds were determined by DPPH radical scavenging, ABTS Cation Radical Decolarization and CUPRAC Cupric Reducing Antioxidant Capacity assay methods. The ABTS cation scavenging assay provided the best responses for the compounds and the candidates 3k and 3l were determined as promising targets for the antioxidant activity. Plausible binding mode and interaction of ligands with the selected enzyme have been studied by molecular docking, supporting the experimental results. In silico ADME showed high drug likeness of the synthesized compounds. © 2024 Elsevier B.V.
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    Synthesis and molecular modeling studies of naphthazarin derivatives as novel selective inhibitors of ?-glucosidase and ?-amylase
    (Elsevier B.V., 2023) Abadan, Şebnem; Sağlam, Mehmet F.; Koca, Mehmet Serdar; Bingül, Murat; Şahin, Hasan; Zorlu, Yunus; Şengül, İbrahim F.
    Diabetes mellitus is known as one of the most life-threatening diseases and has attracted the attention of medicinal chemists. The design and synthesis of novel potential candidates for the inhibition of αamylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates are an important approach for the treatment of diabetes. In this current work, a range of novel mono and naphthazarin derivatives were successfully synthesized by the esterification reaction of naphthazarin with different benzoyl chlorides and heterocyclic acyl chlorides. The synthesized compounds were subjected to in vitro antidiabetic activities through α-glucosidase and α-amylase inhibition properties. Despite the limited inhibition potential against α-amylase enzymes, naphthazarin derivatives would be promising targets for antidiabetic study due to the specificity for α-glucosidase enzyme. The compound 18 revealed a dual inhibition behavior, however all the other active compounds were detected as specific for α-glucosidase inhibition and quite potent compared to the standard acarbose which is promising for eliminating the side effects associated with the non-selectivity of acarbose. The compound 19 was the best candidate for inhibition with IC50 value of 7.4 μM and resulted 150-fold better activity compared to the standard. Free energy calculations support the experimental binding affinity of compound 19 found as the most promising drug candidate for α-glucosidase among the synthesized compounds. The plausible binding mode and the interaction of compound 19 complexed with α-glucosidase has been revealed by MD simulations.
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    Synthesis, biologic properties, and molecular modeling studies of bis-indole based thiosemicarbazones
    (Springer, 2024) Ceyhan, Sadık M.; Bingül, Murat; Şahin, Hasan; Boǧa, Mehmet; Sağlam, Mehmet F.; Kandemir, Hakan; Şengül, İbrahim Fazıl
    The Schiff base condensation reaction of thiosemicarbazides and methylene bridged 2,2′-bisindolylmethanes, prepared from the acid-catalyzed condensation of 3-aryl-4,6-dimethoxyindole-7-carbaldehydes and formaldehyde, produced a series of the targeted bis-indole based thiosemicarbazones. To explore the biological potential of the newly synthesized compounds, antidiabetic, anticholinesterase, and antioxidant activities were investigated. The structural derivatization carried out by the addition of bromophenyl ring at C3 position of the indole backbone increased the enzyme potency towards the anticholinesterase activity. Some of the targeted compounds showed selective the α-glucosidase enzyme inhibition activity. In addition to that, the inhibition concentrations were found to lower that the standard acarbose showing that they may be more efficient agents. Although most of the compounds were effective for the metal chelation capacities (CUPRAC), a couple of examples were found to be favorable for DPPH and ABTS assays. The presence of methyl substituted thiosemicarbazone tail with different indole back bones individually detected as promising targets for ABTS and DPPH activities. The compound methyl substituted thiosemicarbazone was also determined as the most potent agent with the 6 μM inhibition concentration toward CUPRAC assay. Molecular docking study was performed to support the experimental results. Graphical abstract: (Figure presented.)