Benzenesulfonamides bearing pyrrolidinone moiety as inhibitors of carbonic anhydrase IX: synthesis and binding studies

Rutkauskas, K.; Zubrienė, Asta; Tumosienė, Ingrida; Kantminienė, Kristina; Mickevičius, Vytautas; Matulis, Daumantas

doi:10.1007/s00044-016-1741-5

Cited by 9 publications

(12 citation statements)

References 30 publications

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“…When studying correlations between compound's chemical structure and observed binding affinity for CA II or CA XII, the studied para‐ substituted benzenesulfonamides bound to CA II with more than ten‐fold higher affinity than to CA XII. The data were consistent with other published studies [42,48,67–69] . Despite the fact that 4‐(4‐fluorophenylureido)benzenesulfonamide U‐104/SLC‐0111 [49] ( 2 in this study) has been tested in patients with advanced solid tumors and has finished Phase 1 clinical trial, [70] our study indicates, that as confirmed by three different assays (FTSA, ITC and SFA), the U‐104/SLC‐0111 exhibits rather weak, micromolar, affinity for anticancer target CA XII and binds it 17‐fold weaker than off‐target CA II.…”

Section: Discussionsupporting

confidence: 91%

“…The data were consistent with other published studies. [42,48,[67][68][69] Despite the fact that 4-(4-fluorophenylureido)benzenesulfonamide U-104/SLC-0111 [49] (2 in this study) has been tested in patients with advanced solid tumors and has finished Phase 1 clinical trial, [70] our study indicates, that as confirmed by three different assays (FTSA, ITC and SFA), the U-104/SLC-0111 exhibits rather weak, micromolar, affinity for anticancer target CA XII and binds it 17-fold weaker than off-target CA II. Recently, Jonsson and Liljas have expressed doubts about proper experimental data for promoting the U-104/SLC-0111 compound into preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

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Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

et al. 2021

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A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti‐cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure‐based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

et al. 2021

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“…(2014, 2015); Rutkauskas et al . (2014, 2017); Zubrienė et al . (2014, 2015, 2017); Kazokaitė et al .…”

Section: A Database Of Intrinsic Affinities Of Sulfonamide Inhibitor mentioning

confidence: 99%

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

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Manakova

et al. 2018

Quart. Rev. Biophys.

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“…Hydrazide 9 was used as a precursor for the synthesis of a number of heterocyclic derivatives. By employing the convenient reaction of acid hydrazides with carbon disulfide in alcohol in the presence of KOH [ 24 , 25 ], 1-(5-chloro-2-hydroxyphenyl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one ( 10 ) was synthesized from hydrazide 9 with carbon disulfide followed by cyclization in situ of the formed potassium salt of hydrazinocarbothioate with hydrochloric acid to pH 3–4. Formation of oxadiazole ring in 10 has been confirmed by the presence of carbon resonances at 164.1 ppm (C=N) and 174.2 ppm (C=S) in the 13 C-NMR spectrum.…”

Section: Resultsmentioning

confidence: 99%

“…Condensation reactions of acid hydrazides with aliphatic diketones provide five-membered heterocyclic compounds [ 25 , 26 ]. Thus, pyrrole derivative 12 was obtained from hydrazide 9 by refluxing it with hexane-2,4-dione in propan-2-ol in the presence of acetic acid for 2 h. Reaction of 9 with pentane-2,5-dione in the presence of concentrated HCl at reflux temperature afforded pyrazole derivative 13 in 82% yield over 5 h. The reaction was much faster (20 min), when the reaction mixture was subjected to microwave irradiation at 100 °C.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 1-(5-Chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives and Their Antioxidant Activity

et al. 2019

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A series of novel 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives containing chloro, hydroxyl, isopropyl, nitro, nitroso, and amino substituents at benzene ring and 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives bearing heterocyclic moieties were synthesized. Antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method and reducing power assay. A number of compounds were identified as potent antioxidants. Antioxidant activity of 1-(5-chloro-2-hydroxyphenyl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one has been tested to be 1.5 times higher than that of a well-known antioxidant ascorbic acid. 1-(5-Chloro-2-hydroxyphenyl)-4-(4-methyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)pyrrolidin-2-one has shown 1.35 times higher antioxidant activity than that of vitamin C by DPPH radical scavenging method and optical density value of 1.149 in reducing power assay. The structure of 1-(5-chloro-2-hydroxyphenyl)-N-(1,3-dioxoisoindolin-2-yl)-5-oxopyrrolidine-3-carboxamide was unambiguously assigned by means of X-ray diffraction analysis data.

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Benzenesulfonamides bearing pyrrolidinone moiety as inhibitors of carbonic anhydrase IX: synthesis and binding studies

Cited by 9 publications

References 30 publications

Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

Synthesis of 1-(5-Chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives and Their Antioxidant Activity

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