In silico and in vitro inhibition abilities of novel benzene sulfonamides on carbonic anhydrase and choline esterases DOI

Sevgi Surgun,

Necla Öztaşkın,

Ahmet Çağan

и другие.

Phosphorus, sulfur, and silicon and the related elements, Год журнала: 2024, Номер 199(5), С. 439 - 451

Опубликована: Май 3, 2024

Compounds that possess a benzene sulfonamide structure are utilized in wide range of fields. It is reported the literature many compounds belonging to this class exhibit various pharmacological properties such as antibacterial, antifungal, antiviral, anticancer, inflammatory, antiglaucoma, and anticholinergic effects. Carbonic anhydrase (CA) enzymes play critical role pH regulation, long-term synaptic turnover therefore thought be associated with diseases mental retardation, Alzheimer's disease (AD) Down syndrome. Studies have there an increase levels hCA-I hCA-II isoenzymes AD. AD complex, multifactorial disorder, so therapy should probably address not only cholinergic system but also additional systems. Based on these features, series novel substituted sulfonamides were synthesized from 1,2,3-trimethoxy-5-methylbenzene. Sulfonyl chloride 9 was reaction 1,2,3-trimethoxy-5-methylbenzene excess chlorosulfonic acid. The obtained sulfonyl NH3 N-alkyl amines, aniline, phenethylamine gave derivatives 10–16. evaluated for their carbonic (hCA I-II), acetyl cholinesterase (AChE) butyryl (BChE) inhibitory properties. Some 10–16 showed effect hCA isoenzymes. Ki values determined I enzyme 102.01–147.19 µM. Benzene AChE BChE. BChE 28.76–308.08 µM 42.80–445.60 µM, respectively. 15–16 selective inhibitors 10 11-fold more selectivity than In addition, in-silico SAR ADME investigated.

Язык: Английский

Discovery of Dual‐Inhibitor Acyl Hydrazones for Acetylcholinesterase and Carbonic Anhydrase I/II: A Mechanistic Insight into Alzheimer's Disease DOI Open Access
Efe Doğukan Dincel, Ebru Didem Kuran, Yeliz Demir

и другие.

ChemistrySelect, Год журнала: 2025, Номер 10(9)

Опубликована: Фев. 28, 2025

Abstract This study presents the synthesis of various non‐sulfonamide acyl hydrazone derivatives intended as multi‐target ligands for treatment Alzheimer's disease. The were thoroughly characterized using advanced spectroscopic techniques and their inhibitory activities against key enzymes, acetylcholinesterase (AChE) human carbonic anhydrase I/II (hCA) systematically assessed. synthesized compounds demonstrated significant suppression hCAs. 4‐methoxycarbonyl compound ( 2a , Ki = 69.74 nM) exhibited a robust effect hCA I compared to reference medication acetazolamide (AAZ, 373.46 nM). 4‐dimethylamino 2b K i 120.36 superior potency AAZ (K 350.66 II. 2,4‐dinitrobenzylidene 2n 69.18 derivative displayed remarkable AChE tacrine (THA, 205.78 Additionally, in silico studies provided insight into binding interactions enhancing understanding potential. identified with varying affinities isoenzymes highlighting potential effective selective inhibitors. reported biological indicating promising lead hCAs AChE.

Язык: Английский

Процитировано

1
New Sulfonate Ester‐Linked Fluorinated Hydrazone Derivatives as Multitarget Carbonic Anhydrase and Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Analysis DOI Creative Commons

Berna Akış,

Reşit Çakmak, Murat Şentürk

и другие.

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(12)

Опубликована: Авг. 19, 2024

Abstract In this study, some new hydrazone derivatives ( 2a – g ) was designed, synthesized for first time, and evaluated as multitarget inhibitors of AChE, BChE, hCA I II. The chemical structures hybrids were confirmed by elemental analysis spectroscopic techniques. All tested compounds showed low nanomolar inhibition with IC 50 values in the range 30.4–264.0 nM against I, 23.2–251.6 II, 12.1–114.3 76.4–134.0 BChE. These inhibited AChE more than acetazolamide (AZA) neostigmine. Among them, 2c 2e , which have a linear structure, determined to be most active inhibitor candidates these selected enzymes. Molecular docking studies carried out on 2a‐ ‐ ), revealing their binding interactions site II thus supporting experimental findings. Additionally, silico absorption, distribution, metabolism, excretion (ADME) prediction obtained approaches determine solubility, whether they potential cross blood‐brain barrier (BBB), such GI absorption drug likeness principles.

Язык: Английский

Процитировано

3
New 4-Methanesulfonyloxy Benzohydrazide Derivatives as Potential Antioxidant and Carbonic Anhydrase I and II Inhibitors: Synthesis, Characterization, Molecular Docking, Dynamics & ADME Studies DOI
Aytekin Köse, Leyla Polat Köse, Halil Şenol

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер unknown, С. 140937 - 140937

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

2
Synthesis, in-vitro inhibition of cholinesterase and in silico studies of new hydrazide-hydrazones derived from Clopidogrel DOI
Fatih Tok,

Taner Çelikçi,

Ahmet Beytullah Acar

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер 1314, С. 138763 - 138763

Опубликована: Май 27, 2024

Язык: Английский

Процитировано

1
In silico and in vitro inhibition abilities of novel benzene sulfonamides on carbonic anhydrase and choline esterases DOI

Sevgi Surgun,

Necla Öztaşkın,

Ahmet Çağan

и другие.

Phosphorus, sulfur, and silicon and the related elements, Год журнала: 2024, Номер 199(5), С. 439 - 451

Опубликована: Май 3, 2024

Compounds that possess a benzene sulfonamide structure are utilized in wide range of fields. It is reported the literature many compounds belonging to this class exhibit various pharmacological properties such as antibacterial, antifungal, antiviral, anticancer, inflammatory, antiglaucoma, and anticholinergic effects. Carbonic anhydrase (CA) enzymes play critical role pH regulation, long-term synaptic turnover therefore thought be associated with diseases mental retardation, Alzheimer's disease (AD) Down syndrome. Studies have there an increase levels hCA-I hCA-II isoenzymes AD. AD complex, multifactorial disorder, so therapy should probably address not only cholinergic system but also additional systems. Based on these features, series novel substituted sulfonamides were synthesized from 1,2,3-trimethoxy-5-methylbenzene. Sulfonyl chloride 9 was reaction 1,2,3-trimethoxy-5-methylbenzene excess chlorosulfonic acid. The obtained sulfonyl NH3 N-alkyl amines, aniline, phenethylamine gave derivatives 10–16. evaluated for their carbonic (hCA I-II), acetyl cholinesterase (AChE) butyryl (BChE) inhibitory properties. Some 10–16 showed effect hCA isoenzymes. Ki values determined I enzyme 102.01–147.19 µM. Benzene AChE BChE. BChE 28.76–308.08 µM 42.80–445.60 µM, respectively. 15–16 selective inhibitors 10 11-fold more selectivity than In addition, in-silico SAR ADME investigated.

Язык: Английский

Процитировано

1