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    Öğe
    Bovine carbonic anhydrase (bCA) inhibitors: Synthesis, molecular docking and theoretical studies of bisoxadiazole-substituted sulfonamide derivatives
    (Elsevier, 2024) Eybek, Abdulbaki; Kaya, Mustafa Oguzhan; Gulec, Ozcan; Demirci, Tuna; Musatat, Ahmad Badreddin; Ozdemir, Oguzhan; Oner, Mine Nazan Kerimak
    This paper describes the in vitro inhibition potential of bisoxadiazole-substituted sulfonamide derivatives (6a-t) against bovine carbonic anhydrase (bCA) after they were designed through computational analyses and evaluated the predicted interaction via molecular docking. First, in silico ADMET predictions and physicochemical property analysis of the compounds provided insights into solubility and permeability, then density functional theory (DFT) calculations were performed to analyse their ionization energies, nucleophilicity, in vitro electron affinity, dipole moments and molecular interactions under vacuum and dimethyl sulfoxide (DMSO) conditions. After calculating the theoretical inhibition constants, IC50 values determined from enzymatic inhibition were found between 12.93 and 45.77 mu M. Molecular docking evaluation revealed favorable hydrogen bonding and pi-interactions of the compounds within the bCA active site. The experimentally most active compound, 6p, exhibited the strongest inhibitory activity with a theoretical inhibition constant value of 9.41 nM and H-bonds with Gln91, Thr198, and Trp4 residues and His63 Pi-cation interactions with His63 residues. Overall, the study reveals promising bCA blocking potential for the synthesized derivatives, similar to acetazolamide.
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    Öğe
    Synthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives
    (Springer, 2024) Kaya, Mustafa Oguzhan; Demirci, Tuna; Calisir, Umit; Ozdemir, Oguzhan; Kaya, Yesim; Arslan, Mustafa
    In this study, the activation of pyruvate kinase enzyme in vitro via different urea substituents in the para position as functional groups of 1,4-dihydropyridine derivatives synthesized by Hantzsch reaction method was investigated. Elemental analysis, 1H-NMR, 13C-NMR and FT-IR spectroscopy were used to identify the ureido phenyl substituted 1,4-dihydropyridine derivatives. Virtual screening based on molecular docking supported the results of possible in vitro pyruvate kinase (PK) activators among the synthesized substances. The results showed that all compounds successfully activated PK. The strongest activator effect was shown by ethyl-4-(4-(4-(3-(3-methoxyphenyl)thioureido)phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,7,8-hexahydroquinolin-3 (7) with an AC50 value of 87.70 mu M. In molecular docking studies, full compatibility (- 3016.93 FF), binding affinities (Delta G = - 8.58 kcal/mol), LUMO-HOMO energy gap (Delta E = 7.85 eV) in Density functional theory (DFT) studies and drug similarity score of the compounds were found to be 0.69. These results shed light on the therapeutic potential of the produced compounds to treat PK-related diseases.
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    Öğe
    Synthesis, inhibition effects, molecular docking and theoretical studies as Paraoxonase 1 (PON1) inhibitors of novel 1,4-dihydropyridine substituted sulfonamide derivatives
    (Springer Birkhauser, 2023) Kaya, Mustafa Oguzhan; Demirci, Tuna; Ozdemir, Oguzhan; Calisir, Umit; Sonmez, Fatih; Arslan, Mustafa
    The novel sulfonamide substitute 1,4-dihydropyridine derivatives were synthesized by the method of Hantzsch reaction. They have been characterized by FT-IR spectroscopy, H-1-NMR, C-13-NMR, and elemental analysis. PON1 which is an antioxidant enzyme has important functions in cardiovascular systems. The enzyme has been purified using a two-step method such as ammonium sulfate precipitation and sepharose-4B-l-tyrosine-9-aminophenanthrene hydrophobic interaction chromatography. The results demonstrated that all the synthesized compounds inhibited PON1 enzyme. The best inhibition effect was observed in compound (1) for PON1 enzyme (IC50: 8.04 mu M, K-i: 5.43 mu M). The free radical scavenging for PON1 was discovered as 20.16 mg/mL, while drug score value was reported as 0.13 for compound (1). Furthermore, the lowest binding energy (-1.31 kcal/mol) determined by molecular docking for PON1 enzyme and the lowest LUMO-HOMO gap ( increment E = 3.12 eV) were calculated for compound (1).