Exploration of 1,2,3-triazole linked benzenesulfonamide derivatives as isoform selective inhibitors of human carbonic anhydrase

Kakakhan, Chnar; Türkeş, Cüneyt; Güleç, Özcan; Demir, Yeliz; Arslana, Mustafa; Özkemahlı, Gizem; Beydemır, Şükrü

doi:10.1016/j.bmc.2022.117111

Cited by 61 publications

(33 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell growth inhibition potentials of novel acetic acid derivatives containing quinazolin‐4(3 H )‐one ring ( 16 and 19 ) were evaluated by the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay as in the previous research (Güleç et al, 2022; Kakakhan et al, 2022; Sever et al, 2021c). After culturing, the cells were plated with 1 × 10 5 cells/well in the 96‐well plate and incubated at 37°C for 24 h. The cells were subsequently treated for 24 h with Compounds 16 and 19 at the indicated concentrations (25, 50, 75, 100, and 200 nM).…”

Section: Methodsmentioning

confidence: 99%

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Tokalı

Demir

Türkeş

et al. 2023

Drug Development Research

Self Cite

View full text Add to dashboard Cite

Aldose reductase (AR) is a crucial enzyme of the polyol pathway through which glucose is metabolized under conditions of hyperglycemia related to diabetes. A series of novel acetic acid derivatives containing quinazolin-4(3H)-one ring (1-22) was synthesized and tested for in vitro AR inhibitory effect. All the target compounds exhibited nanomolar activity against the target enzyme, and all compounds displayed higher activity as compared to the reference drug epalrestat.Among them, Compound 19, named 2-(4-[(2-[(4-methylpiperazin-1-yl)methyl]-4oxoquinazolin-3(4H)-ylimino)methyl]phenoxy)acetic acid, displayed the strongest inhibitory effect with a K I value of 61.20 ± 10.18 nM. Additionally, these compounds were investigated for activity against L929, nontumoral fibroblast cells, and MCF-7, breast cancer cells using the MTT assay. Compounds 16 and 19 showed lower toxicity against the normal L929 cells. The synthesized compounds' (1-22) absorption, distribution, metabolism, and excretion properties were also evaluated.Molecular docking simulations were used to look into the possible binding mechanisms of these inhibitors against AR.

show abstract

Section: Methodsmentioning

confidence: 99%

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Tokalı

Demir

Türkeş

et al. 2023

Drug Development Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Small‐Molecule Drug Discovery Suite 2022‐2 for Mac, which includes the Maestro V13.1, [ 63 ] QikProp V7.1, [ 64 ] Protein Preparation Wizard, [ 65 ] SiteMap, [ 66 ] LigPrep, [ 67 ] Receptor Grid Generation, [ 68 ] and Ligand Docking (Schrödinger, LLC), was used to perform ADME and molecular docking calculations, as previously reported. [ 69,70 ] Protein Data Bank (http://www.rcsb.org/) was used to obtain the crystal structures of h CAs (PDB code 1AZM for h CA I; resolution: 2.00 Å; species: Homo sapiens [ 71 ] and PDB code 2H4N for h CA II; resolution: 1.90 Å; species: Homo sapiens [ 72 ] ), and AChE (PDB code 7E3I; resolution: 2.85 Å; species: Homo sapiens ). The Protein Preparation Wizard in the Maestro panel [ 73 ] was used to optimize proteins 1AZM, 2H4N, and 7E3I structurally.…”

Section: Methodsmentioning

confidence: 99%

Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

Demir

Türkeş

Çavuş

et al. 2022

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

New Schiff base-bearing thiosemicarbazones (1-13) were obtained from 4-hydroxy-3, 5-dimethoxy benzaldehyde and various isocyanates. The structures of the synthesized molecules were elucidated in detail. Density functional theory calculations were also performed to determine the spectroscopic properties of the compounds. Moreover, the enzyme inhibition activities of these compounds were investigated. They showed highly potent inhibition effects on acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) (K I values are in the range of 51.11 ± 6.01 to 278.10 ± 40.55 nM, 60.32 ± 9.78 to 300.00 ± 77.41 nM, and 64.21 ± 9.99 to 307.70 ± 61.35 nM for AChE, hCA I, and hCA II, respectively). In addition, molecular docking studies were performed, confirmed by binding affinities studies of the most potent derivatives.

show abstract

“…The MM‐GBSA binding energies, [107] which predict relative binding affinities for these phenolic agents, were calculated using the VSGB energy model [108] and the OPLS4 force field [109] . The analysis of the molecular interactions was performed on the Maestro interface (Figures 6,7, S5, and S6) [110–112] …”

Section: Methodsmentioning

confidence: 99%

“…[109] The analysis of the molecular interactions was performed on the Maestro interface (Figures 6,7, S5, and S6). [110][111][112]…”

Section: Chemistryselectmentioning

confidence: 99%

In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors**

2022

Self Cite

View full text Add to dashboard Cite

Polyol pathway enzymes, aldose reductase (EC 1.1.1.21; AR, ALR2), and sorbitol dehydrogenase (EC 1.1.1.14; SDH, SORD) have been widely investigated as the enzymes crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although phenolic compounds have been reported to possess many other biological activities, in continuation of our interest in designing and discovering potent inhibitors of AR and SDH, herein, we have evaluated these agents’ inhibitory potential against polyol pathway enzymes. Our in vitro studies revealed that all the derivatives show activity against recombinant human AR (rhAR) and SDH (rhSDH), with KI constants ranging from 9.37±0.16 μM to 77.22±2.49 μM and 2.51±0.10 μM to 42.16±1.03 μM, respectively. Among these agents, Prunetin and Phloridzin showed prominent inhibitory activity versus rhAR and rhSDH, while some were also determined to possess perfect dual activity. Moreover, in silico studies were also performed to rationalize binding site interactions of these agents with the target enzyme AR and SDH. According to ADME‐Tox was also determined that these derivatives be agents exhibiting suitable drug‐like properties. The compounds identified therapeutic potentials in this study may be promising for developing lead therapeutic agents to prevent polyol pathway complications.

show abstract

Exploration of 1,2,3-triazole linked benzenesulfonamide derivatives as isoform selective inhibitors of human carbonic anhydrase

Cited by 61 publications

References 79 publications

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors**

Contact Info

Product

Resources

About