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New 1H-indole-2,3-dione 3-thiosemicarbazones with 3-sulfamoylphenyl moiety as selective carbonic anhydrase inhibitors

dc.contributor.authorEraslan-Elma, Pinar
dc.contributor.authorAKDEMİR, ATİLLA
dc.contributor.authorBerrino, Emanuela
dc.contributor.authorBozdag, Murat
dc.contributor.authorSupuran, Claudiu T.
dc.contributor.authorKarali, Nilgun
dc.contributor.institutionauthorAKDEMİR, ATİLLA
dc.date.accessioned2022-05-17T20:59:26Z
dc.date.available2022-05-17T20:59:26Z
dc.date.issued2022-05-01T00:00:00Z
dc.description.abstract1-Methyl/ethyl/benzyl-5-(un)substituted 1H-indole-2,3-diones (2, 3, and 4) were synthesized by reaction of 5-(un)substituted 1H-indole-2,3-diones (1) with methyl iodide, ethyl chloride, and benzyl bromide. (3-Sulfamoylphenyl)isothiocyanate (6) was obtained by the treatment of 3-aminobenzenesulfonamide (5) with thiophosgene. Compound 6 was reacted with hydrazine to yield 4-(3-sulfamoylphenyl)thiosemicarbazide (7). Novel 1-(un)substituted/methyl/ethyl/benzyl-5-(un)substituted 1H-indole-2,3-dione 3-[4-(3-sulfamoylphenyl)thiosemicarbazone] derivatives (8-11) were prepared by condensation of 7 and 1-4. The structures of the synthesized compounds were confirmed by elemental analysis and spectral data. Inhibition of the widely distributed cytosolic off-targets human carbonic anhydrases (hCAs) I and II, and two tumor-associated membrane-bound isoforms (hCAs IX and XII), by 8-11 was investigated. The hCA II inhibitory effects of all tested compounds were in the subnanomolar to low nanomolar levels (K-i = 0.32-83.3 nM), and generally high selectivity for hCA II isoenzyme over hCA I, IX, and XII isoenzymes was observed. The strongest inhibitors of hCA II, 1-benzyl-5-(trifluoromethoxy)-substituted 11c (K-i = 0.32 nM) and 1-ethyl-5-chloro-substituted 10e (K-i = 0.35 nM), were docked within the enzyme active site. Molecular modeling studies with the most effective hCA IX and XII inhibitors were also carried out.
dc.identifier.citationEraslan-Elma P., AKDEMİR A., Berrino E., Bozdag M., Supuran C. T. , Karali N., -New 1H-indole-2,3-dione 3-thiosemicarbazones with 3-sulfamoylphenyl moiety as selective carbonic anhydrase inhibitors-, ARCHIV DER PHARMAZIE, 2022
dc.identifier.doi10.1002/ardp.202200023
dc.identifier.pubmed35500156
dc.identifier.scopus85129260476
dc.identifier.urihttp://hdl.handle.net/20.500.12645/30614
dc.identifier.wosWOS:000789602400001
dc.titleNew 1H-indole-2,3-dione 3-thiosemicarbazones with 3-sulfamoylphenyl moiety as selective carbonic anhydrase inhibitors
dc.typeArticle
dspace.entity.typePublication
local.avesis.id5c34cfb0-5c26-4b88-a6ee-ca8987c420de
local.publication.isinternational1
relation.isAuthorOfPublication19bc513a-c695-4e72-ba1d-83b8d6c574c8
relation.isAuthorOfPublication.latestForDiscovery19bc513a-c695-4e72-ba1d-83b8d6c574c8
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