Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes

Najm, Mazin A.A.; Mahmoud, Walaa R.; Taher, Azza T.; Abbas, Samir Y.; Awadallah, Fadi M.; Allam, Heba Abdelrasheed; Vullo, Daniela; Supuran, Claudiu T.

doi:10.1080/14756366.2022.2126463

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…The synthetic route to obtain the target compounds reported here is outlined in Scheme 2 . The 4-thioureidobenzenesulphonamide intermediate 6 , prepared according to the literature procedure 12 , 13 was upon treatment of sulphanilamide 5 with KSCN in a refluxing aqueous solution of HCl. The target alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates 8a–o were selectively synthesised by reaction of 4-thioureidobenzenesulphonamide 6 with the corresponding alkyl/benzyl halides 7 at elevated temperatures.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibitor and enzyme solutions were preincubated together for 6 h at room temperature prior to assay in order to allow for the formation of the E – I complex. The inhibition constants were obtained by nonlinear least-squares methods using PRISM 3 and the Cheng–Prusoff equation, as reported earlier 12 , 13 , 20 , 21 , and represent the mean from at least three different determinations. All CA isoforms were recombinant ones obtained in-house as reported earlier 22 , 23 and their concentrations in the assay system ranged between 7.6–12.5 nM.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors

Abdoli

Bonardi

Supuran

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A library of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates was synthesised by selective S -alkylation of the easily accessible 4-thioureidobenzenesulphonamide. The compounds were assayed as inhibitors of four human (h) carbonic anhydrase isoforms hCA I, II, VII, and XIII, as well as three bacterial enzymes belonging to the β-CA class, MscCA from Mammaliicoccus ( Staphylococcus ) sciuri and StCA1 and StCA2, from Salmonella enterica (serovar Typhimurium ). Most compounds investigated here exhibited moderate to low nanomolar inhibition constants against hCA I, II, and VII. The cytosolic hCA XIII was also inhibited by these compounds, but not as effective as hCA I, II, and VII. Several compounds were very effective against MscCA and StCA1. StCA2 was less inhibited compared to MscCA and StCA1. Some compounds showed considerable selectivity for inhibiting some CA isoforms. They may thus be considered as interesting starting points for the discovery and development of novel therapeutic agents belonging to this class of enzyme inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Experimental Protocolsmentioning

confidence: 99%

Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors

Abdoli

Bonardi

Supuran

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Inhibitor and enzyme solutions were preincubated together for 15 min at room temperature prior to assay in order to allow for the formation of the E–I complex. The inhibition constants were obtained by nonlinear least-squares methods using PRISM 3 and the Cheng–Prusoff equation, as reported earlier ,,,,− and represent the mean from at least three different determinations. All CA isoforms were recombinant ones obtained in-house as reported earlier, − and their concentrations in the assay system ranged between 7.6 and 12.5 nM.…”

Section: Ca Inhibitory Assaymentioning

confidence: 99%

Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect

et al. 2023

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Here, we report for the first time a series of sulfonamide derivatives with scaffolds bearing flexible moieties, namely, rotamers or tropoisomers capable of adapting their geometry in the active center of enzymes thus being effective and selective carbonic anhydrase (CAs, EC 4.2.1.1) enzyme inhibitors. All compounds exhibited effective in vitro inhibition activity toward the main hCA isoforms related to cancer (i.e., hCA II, hCA IX, and hCA XII with K I values in the low nanomolar range). Three selected compounds showed a great cytotoxic effect on cancer cell lines ex vivo. X-ray crystallographic experiments assessed the binding modes of compound 35 with active centers of hCA IX and hCA XII.

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“…41,42 To evaluate if any of the selection procedures led to the identification of potentially isoform-selective inhibitors, we also determined the Ki values for the carbonic anhydrase IX (hCA IX) (Table 1). 43 12.1 25.7 2…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

Identification of specific carbonic anhydrase inhibitors via in situ click chemistry, phage-display and synthetic peptide libraries: comparison of the methods and structural study

et al. 2023

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Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes

Cited by 7 publications

References 41 publications

Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors

Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors

Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect

Identification of specific carbonic anhydrase inhibitors via in situ click chemistry, phage-display and synthetic peptide libraries: comparison of the methods and structural study

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