Exploration of Some Bis‐Sulfide and Bis‐Sulfone Derivatives as Non‐Classical Aldose Reductase İnhibitors

ChemistrySelect, Год журнала: 2023, Номер 8(5)

Опубликована: Фев. 2, 2023

Abstract Aldose reductase (AR, ALR2; EC 1.1.1.21), an enzyme that converts glucose to fructose on the polyol pathway, is important member of Aldo‐keto superfamily. ALR2 part rate‐limiting step, which associated with diabetic complications in this process, and plays a role regulating reactive oxygen species induced by growth factors cytokines. Despite fact sulfides sulfones have been discovered variety other biological functions, current study, we assessed inhibitory potential derivatives bis‐sulfide ( 5 – i ) bis‐sulfone 6 order further our interest designing discovering powerful inhibitors. The results investigations showed all exhibit activity against ALR2, K I values ranging from 0.53±0.03 4.20±0.06 μM. Among these agents, 2,6‐bis((4‐chlorophenyl)(phenylthio)methyl)cyclohexan‐1‐one h ), 2,6‐bis((3‐nitrophenyl)(phenylthio)methyl)cyclohexan‐1‐one c 2,6‐bis((3‐chlorophenyl)(phenylthio)methyl)cyclohexan‐1‐one g exhibited prominent constants μM, 0.65±0.04 0.71±0.05 respectively, were found be more potent than epalrestat =0.79±0.01 μM) currently, only inhibitor (ALR2I) utilized treatment. Additionally, silico molecular docking experiments carried out explain how bis‐sulfides bis‐sulfones interacted target ALR2′s binding site. According ADME‐Tox compounds are predicted ALR2Is appropriate drug‐like characteristics. study‘s findings could exploited create innovative therapeutics prevent diabetes complications.

Язык: Английский

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Calcium Channel Blockers: The Effect of Glutathione S‐Transferase Enzyme Activity and Molecular Docking Studies

ChemistrySelect, Год журнала: 2021, Номер 6(40), С. 11137 - 11143

Опубликована: Окт. 26, 2021

Abstract Recently, as a drug target in cancer treatment, the superfamily of glutathione S‐transferase (GSTs, EC 2.5.1.18) have been invited considerable interest by scientists. In particular, they are overexpressed many human cell lines, GSTs can catalyze conjugation cellular nucleophile (GSH) with wide range electrophilic carcinogens toxins and drugs, meanwhile producing oxidative stress. For this purpose, GST was purified GSH‐agarose affinity chromatography, some calcium channel blockers (CCBs), such amlodipine, cinnarizine, isradipine, nifedipine, nilvadipine, were assessed for their inhibitory actions against GST. The CCBs demonstrated micromolar levels activity towards ( K I s spanning within 98.84±0.53 μM–502.70±2.53 μM range). best observed isradipine. Additionally, molecular docking study performed competitive inhibitor nilvadipine on to describe possible interaction active site confirm activity.

Язык: Английский

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Dual functional cholinesterase and carbonic anhydrase inhibitors for the treatment of Alzheimer's disease: Design, synthesis, in vitro, and in silico evaluations of coumarin-dihydropyridine derivatives

Journal of Molecular Structure, Год журнала: 2022, Номер 1276, С. 134767 - 134767

Опубликована: Дек. 8, 2022

Язык: Английский

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Biological evaluation and in silico study of benzohydrazide derivatives as paraoxonase 1 inhibitors

Journal of Biochemical and Molecular Toxicology, Год журнала: 2022, Номер 36(11)

Опубликована: Авг. 2, 2022

Serum paraoxonase 1 (PON1) is found in all mammalian species and a calcium-dependent hydrolytic enzyme. PON1 hydrolyze several substrates, including carbonates, esters, organophosphates. In the current study, we aimed to investigate effect of presynthesized benzohydrazide derivatives (1-9) on activity. Benzohydrazide compounds moderate inhibited with half-maximal inhibitory concentration values ranging from 76.04 ± 13.51 221.70 13.59 μM KI 38.75 12.21 543.50 69.76 μM. Compound 4 (2-amino-4-chlorobenzohydrazide) showed best inhibition (KI = μM). Molecular docking ADME-Tox studies were also carried out. this context, hope that results obtained study contribute determination side effects new benzohydrazide-based pharmacological be developed.

Язык: Английский

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Design, synthesis, spectroscopic characterizations,in vitropancreatic lipase as well as tyrosinase inhibition evaluations andin silicoanalysis of novel aryl sulfonate-naphthalene hybrids

Journal of Biomolecular Structure and Dynamics, Год журнала: 2022, Номер 41(15), С. 7128 - 7143

Опубликована: Сен. 7, 2022

One of the primary purposes this study is to synthesize new aryl sulfonate-naphthalene hybrid structures possessing divergent electron-withdrawing and electron-releasing functional groups. Following improved reaction conditions, we successfully gathered ten distinct sulfonate derivatives (3a-j) with good yields. The synthesized naphthalene-based were then characterized using appropriate analytical methods (FT-IR, 1H-NMR, 13C-NMR, HRMS, elemental analysis). Additionally, in vitro silico enzyme inhibitory properties prepared evaluated against pancreatic lipase tyrosinase enzymes. Corresponding activity investigations revealed that produced compounds inhibit enzymes significantly. According lowest IC50 values, 3h (95.3 ± 4.0 µM) demonstrated most effective inhibition lipase, whereas 3a (40.8 3.3 was found as tyrosinase. studies, exhibited highest affinity value (-9.9 kcal/mol) 3f best (-8.7 tyrosinase.Furthermore, investigated various structural physicochemical target molecules, namely frontier orbital' (HOMO, LUMO, bandgap) energies (including their corresponding contour plots), global reactivity descriptors (ionization energy electron affinity), electronegativity values from ground-state (GS) density theory (DFT) calculations. These observed electrostatic interactions effectively contributed studied molecules' experimentally potential. Also, ADMET studies enlighten molecular enzymes.Communicated by Ramaswamy H. Sarma.

Язык: Английский

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