Design, synthesis, spectroscopic characterizations,in vitropancreatic lipase as well as tyrosinase inhibition evaluations andin silicoanalysis of novel aryl sulfonate-naphthalene hybrids DOI
Adem Korkmaz, Gülbin Kurtay, Esin Kaya

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(15), P. 7128 - 7143

Published: Sept. 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.

Language: Английский

Synthesis and inhibition profiles of N-benzyl- and N-allyl aniline derivatives against carbonic anhydrase and acetylcholinesterase – A molecular docking study DOI Creative Commons
Ibadulla Mahmudov, Yeliz Demir, Yusuf Sert

et al.

Arabian Journal of Chemistry, Journal Year: 2021, Volume and Issue: 15(3), P. 103645 - 103645

Published: Dec. 22, 2021

The alkyl and aryl derivatives of aniline are important starting materials in fine organic synthesis. Allyl bromide benzyl chloride were taken as substrates for the alkylation reaction a halide ion scavenger. Triethylamine was utilized at reflux condition N,N-dimethylacetamide (DMA). Novel synthesized N-benzyl N-allyl (1a-f) evaluated to be highly potent inhibitors acetylcholinesterase (AChE) carbonic anhydrases (hCAs). half maximal inhibitory concentration (IC50) N-benzyl- calculated between 243.11 633.54 nM hCA I, 296.32–518.37 II 182.45–520.21 AChE enzymes. On other hand, Ki values range 149.24 ± 15.59 519.59 102.27 AChE, 202.12 16.21 635.31 45.33 I 298.57 94.13 511.18 115.98 isoenzyme. Additionally, silico molecular docking computations performed with Autodock Vina program support experimental vitro studies both hCAs inhibitors. results demonstrated that scores good agreement results.

Language: Английский

Citations

108
Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif DOI Open Access
Özcan Güleç, Cüneyt Türkeş, Mustafa Arslan

et al.

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

Published: April 9, 2022

Language: Английский

Citations

80
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 DOI

Sercan Askin,

Hakan Tahtacı, Cüneyt Türkeş

et al.

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

Published: May 23, 2021

Language: Английский

Citations

98
Molecular docking and inhibition studies of vulpinic, carnosic and usnic acids on polyol pathway enzymes DOI
Yeliz Demir, Hamid Ceylan, Cüneyt Türkeş

et al.

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

Citations

81
Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors DOI
Cüneyt Türkeş, Süleyman Akocak, Mesut Işık

et al.

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

Citations

77
Transition‐Metal Complexes of Bidentate Schiff‐Base Ligands: In Vitro and In Silico Evaluation as Non‐Classical Carbonic Anhydrase and Potential Acetylcholinesterase Inhibitors DOI
Ümit Yaşar, İlyas Gönül, Cüneyt Türkeş

et al.

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

Citations

72
Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds DOI
Belgin Sever, Cüneyt Türkeş, Mehlika Dilek Altıntop

et al.

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

Citations

72
Biological effects of bis-hydrazone compounds bearing isovanillin moiety on the aldose reductase DOI
Gönül Yapar, Hatice Esra Duran, Nebih Lolak

et al.

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

Published: Nov. 8, 2021

Language: Английский

Citations

62
Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors DOI
Yeliz Demir, Feyzi Sinan Tokalı, Erbay Kalay

et al.

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

Published: Sept. 14, 2022

Language: Английский

Citations

57
Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors DOI
Nebih Lolak, Süleyman Akocak, Mustafa Durgun

et al.

Molecular Diversity, Journal Year: 2022, Volume and Issue: 27(4), P. 1735 - 1749

Published: Sept. 22, 2022

Language: Английский

Citations

49