scholarly journals Indole-Based Hydrazones Containing A Sulfonamide Moiety as Selective Inhibitors of Tumor-Associated Human Carbonic Anhydrase Isoforms IX and XII

2019 ◽  
Vol 20 (9) ◽  
pp. 2354 ◽  
Author(s):  
Kübra Demir-Yazıcı ◽  
Silvia Bua ◽  
Nurgül Mutlu Akgüneş ◽  
Atilla Akdemir ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Carbonic Anhydrase ◽  
Enzyme Inhibition ◽  
Active Sites ◽  
Selective Inhibitors ◽  
Binding Interactions ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Human Carbonic Anhydrase

Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII over hCA I and II. Six compounds showed KI values lower than 10 nM against hCA IX or XII. Molecular modeling studies were performed to suggest binding interactions between the ligand and the hCA active sites.

Novel hydrazido benzenesulfonamides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies

2018 ◽  
Vol 157 ◽  
pp. 28-36 ◽  
Author(s):  
Mahmoud F. Abo-Ashour ◽  
Wagdy M. Eldehna ◽  
Alessio Nocentini ◽  
Hany S. Ibrahim ◽  
Silvia Bua ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
Modeling Studies ◽  
Molecular Modeling Studies

scholarly journals Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII

2019 ◽  
Vol 20 (5) ◽  
pp. 1208 ◽  
Author(s):  
Kerem Buran ◽  
Silvia Bua ◽  
Giulio Poli ◽  
F. Önen Bayram ◽  
Tiziano Tuccinardi ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Carbonic Anhydrase ◽  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Carbonic Anhydrase Ix ◽  
Specific Mechanism ◽  
Single Digit ◽  
Molecular Modeling Studies ◽  
Human Carbonic Anhydrase ◽  
Substituted Coumarins

A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.

scholarly journals Molecular modeling studies of quinazolinone derivatives as novel PI3Kδ selective inhibitors

RSC Advances ◽  
2017 ◽  
Vol 7 (89) ◽  
pp. 56344-56358 ◽  
Author(s):  
Xiu Xiu Peng ◽  
Kai Rui Feng ◽  
Yu Jie Ren
Keyword(s):  
Molecular Modeling ◽  
Pharmacophore Model ◽  
Modeling Method ◽  
Selective Inhibitors ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Quinazolinone Derivatives

The main molecular modeling method, the docking results of newly designed compoundD04and the best pharmacophore model are reported herein.

Synthesis, molecular modeling and cholinesterase inhibitory effects of 2-indolinone-based hydrazinecarbothioamides

2021 ◽  
Author(s):  
Kübra Demir-Yazıcı ◽  
Çağla Begüm Apaydın ◽  
Özge Soylu-Eter ◽  
Nurten Özsoy ◽  
Nilgün Karalı
Keyword(s):  
Molecular Modeling ◽  
Active Site ◽  
Inhibitory Effects ◽  
Binding Interactions ◽  
Modeling Studies ◽  
Ring Method ◽  
Molecular Modeling Studies ◽  
Further Development ◽  
Pharmacophore Group

Background: 2-Indolinone-based hydrazinecarbothioamides carrying a 3-phenylsulfonamide moiety (7–9) were designed by replacement of donepezil's pharmacophore group indanone with a 2-indolinone ring. Method: Compounds 7–9 were synthesized by reaction of N-(3-sulfamoylphenyl)hydrazinecarbothioamide (6) with 1 H-indolin-2,3-diones (1–3). Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects of compounds 7–9 were assayed. Molecular modeling studies of 5-chloro-1,7-dimethyl-substituted compound 8e were carried out to determine the possible binding interactions at the active site of AChE. Results: Compound 8e showed the strongest inhibition against AChE ( Ki = 0.52 ± 0.11 μM) as well as the highest selectivity (SI = 37.69). The selectivity for AChE over BuChE of compound 8e was approximately 17-times higher than donepezil and 26-times higher than galantamine. Conclusion: Further development of compounds 7–9 may present new promising agents for Alzheimer's treatment.

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