Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif

Molecular Diversity, Journal Year: 2022, Volume and Issue: 26(5), P. 2825 - 2845

Published: April 9, 2022

Language: Английский

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Discovery of novel benzenesulfonamides incorporating 1,2,3-triazole scaffold as carbonic anhydrase I, II, IX, and XII inhibitors

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 239, P. 124232 - 124232

Published: March 29, 2023

Language: Английский

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Design, synthesis, characterization, in vitro and in silico evaluation of novel imidazo[2,1-b][1,3,4]thiadiazoles as highly potent acetylcholinesterase and non-classical carbonic anhydrase inhibitors

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 113, P. 105009 - 105009

Published: May 23, 2021

Language: Английский

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Molecular docking and inhibition studies of vulpinic, carnosic and usnic acids on polyol pathway enzymes

Journal of Biomolecular Structure and Dynamics, Journal Year: 2021, Volume and Issue: 40(22), P. 12008 - 12021

Published: Aug. 23, 2021

Aldose reductase (AR) and sorbitol dehydrogenase (SDH) are important enzymes of the polyol pathway. In current study, inhibitory effects vulpinic acid (VA) carnosic (CA) usnic (UA) on purified AR SDH were determined. These inhibition could be essential to prevent diabetic complications. from sheep kidney. Then, VA, CA UA tested in various concentrations against these activity vitro. KI values found as 1.46 ± 0.04, 5.13 0.25 11.71 0.27 μΜ for UA, respectively, AR. constants 15.32 0.34, 145.60 2.17 213.40 2.64 SDH. findings indicate that useful treatment complications.Communicated by Ramaswamy H. Sarma

Language: Английский

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Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

Journal of Biomolecular Structure and Dynamics, Journal Year: 2021, Volume and Issue: 40(19), P. 8752 - 8764

Published: May 5, 2021

The underlying cause of many metabolic diseases is abnormal changes in enzyme activity metabolism. Inhibition enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) α-glucosidase (α-GLY) one the accepted approaches treatment Alzheimer's disease (AD) diabetes mellitus (DM). Here we reported an investigation a new series novel ureido-substituted derivatives with sulfamethazine backbone (2a-f) for inhibition AChE, BChE, α-GLY. All demonstrated nanomolar levels α-GLY inhibitors KI values range 56.07-204.95 nM, 38.05-147.04 12.80-79.22 respectively. Among strong N-(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide detected against ChEs, compound 2c, 4-fluorophenylureido derivative, most potent profile towards BChE. A comprehensive ligand/receptor interaction prediction was performed silico three providing molecular docking using Glide XP, MM-GBSA, ADME-Tox modules. present research reinforces rationale behind utilizing innovative anticholinergic antidiabetic agents mechanism action, submitting propositions rational design synthesis targeting ChEs α-GLY.Communicated by Ramaswamy H. Sarma.

Language: Английский

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Transition‐Metal Complexes of Bidentate Schiff‐Base Ligands: In Vitro and In Silico Evaluation as Non‐Classical Carbonic Anhydrase and Potential Acetylcholinesterase Inhibitors

ChemistrySelect, Journal Year: 2021, Volume and Issue: 6(29), P. 7278 - 7284

Published: Aug. 2, 2021

Abstract Schiff bases display superior features for many areas, such as significant intermediates in industrial biological, pharmacological, catalytic and optical properties, organic synthesis, coordination chemistry. The pre‐synthesized two base ligands ( HL 1 2 ) their bidentate metal complexes Co(L , Cu L Ni were tested inhibition activities on acetylcholinesterase (AChE) human carbonic anhydrase h CA I II) isoforms. transition of displayed the potent effect with K constants ranging from 16.39±0.15 to 88.63±0.27 nM 9.32±0.13 33.66±0.57 isoenzymes AChE, respectively. compound AChE II had highest inhibitory effect. Besides, molecular docking analyses most active performed understand binding interactions enzymes’ sites. According both vitro silico analysis results, all compounds potential inhibitors I, isoenzymes.

Language: Английский

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Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

Archiv der Pharmazie, Journal Year: 2021, Volume and Issue: 354(12)

Published: Sept. 27, 2021

New hybrid thiazolyl-pyrazoline derivatives (4a-k) were obtained through a facile and versatile synthetic procedure, their inhibitory effects on the human carbonic anhydrase (hCA) isoforms I II as well acetylcholinesterase (AChE) determined. All new thiazolyl-pyrazolines showed activity at nanomolar levels hCA I, II, AChE inhibitors, with KI values in range of 13.35-63.79, 7.01-115.80, 17.89-48.05 nM, respectively. 1-[4-(4-Cyanophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4f) 1-(4-phenylthiazol-2-yl)-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4a) against hCAs 1-[4-(4-chlorophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4d) 1-[4-(4-nitrophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4b) identified highly potent superior to standard drugs, acetazolamide tacrine, Compounds 4a-k also evaluated for cytotoxic L929 mouse fibroblast (normal) cell line. Moreover, comprehensive ligand-receptor interaction prediction was performed using ADME-Tox, Glide XP, MM-GBSA modules Schrödinger Small-Molecule Drug Discovery Suite elucidate potential binding modes inhibitors these metabolic enzymes.

Language: Английский

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Insights into Manganese Superoxide Dismutase and Human Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15893 - 15893

Published: Dec. 14, 2022

Redox equilibria and the modulation of redox signalling play crucial roles in physiological processes. Overproduction reactive oxygen species (ROS) disrupts body's antioxidant defence, compromising homeostasis increasing oxidative stress, leading to development several diseases. Manganese superoxide dismutase (MnSOD) is a principal enzyme that protects cells from damage by converting anion radicals hydrogen peroxide mitochondria. Systematic studies have demonstrated MnSOD plays an indispensable role multiple This review focuses on preclinical evidence describes mechanisms diseases accompanied with imbalanced status, including fibrotic diseases, inflammation, diabetes, vascular neurodegenerative cancer. The potential therapeutic effects activators mimetics are also discussed. Targeting this specific radical scavenger may be clinically beneficial strategy, understanding provide positive insight into preventing treating related

Language: Английский

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Biological effects of bis-hydrazone compounds bearing isovanillin moiety on the aldose reductase

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 117, P. 105473 - 105473

Published: Nov. 8, 2021

Language: Английский

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Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors

Molecular Diversity, Journal Year: 2022, Volume and Issue: 27(4), P. 1713 - 1733

Published: Sept. 14, 2022

Language: Английский

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