Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives
A series of new derivatives was prepared by derivatisation of the 7-amino moiety present in 7-amino-3,4-dihydroquinolin-2(1H)-one, a compound investigated earlier as CAI. The derivatisation was achieved by: i) reaction with arylsulfonyl isocyanates/aryl isocyanates; (ii) reaction with fluorescein is...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2017.1337759 |
| _version_ | 1819275027303890944 |
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| author | Murat Bozdag Silvia Bua Sameh M. Osman Zeid AlOthman Claudiu T. Supuran |
| author_facet | Murat Bozdag Silvia Bua Sameh M. Osman Zeid AlOthman Claudiu T. Supuran |
| author_sort | Murat Bozdag |
| collection | DOAJ |
| description | A series of new derivatives was prepared by derivatisation of the 7-amino moiety present in 7-amino-3,4-dihydroquinolin-2(1H)-one, a compound investigated earlier as CAI. The derivatisation was achieved by: i) reaction with arylsulfonyl isocyanates/aryl isocyanates; (ii) reaction with fluorescein isothiocyanate; (iii) condensation with substituted benzoic acids in the presence of carbodiimides; (iv) reaction with 2,4,6-trimethyl-pyrylium tetrafluoroborate; (v) reaction with methylsulfonyl chloride and (vi) reaction with maleic anhydride. The new compounds were assayed as inhibitors of four carbonic anhydrases (CA, EC 4.2.1.1) human (h) isoforms of pharmacologic relevance, the cytosolic hCA I and II, the membrane-anchored hCA IV and the transmembrane, tumour-associated hCA IX. hCA IX was the most inhibited isoform (KIs ranging between 243.6 and 2785.6 nm) whereas hCA IV was not inhibited by these compounds. Most derivatives were weak hCA I and II inhibitors, with few of them showing KIs < 10 µm. Considering that the inhibition mechanism with these lactams is not yet elucidated, exploring a range of such derivatives with various substitution patterns may be useful to identify leads showing isoform selectivity or the desired pharmacologic action. |
| first_indexed | 2024-12-23T23:17:48Z |
| format | Article |
| id | doaj.art-3921d1fcbdac4a6f8304411e22c23434 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-23T23:17:48Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-3921d1fcbdac4a6f8304411e22c234342022-12-21T17:26:26ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742017-01-0132188589210.1080/14756366.2017.13377591337759Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivativesMurat Bozdag0Silvia Bua1Sameh M. Osman2Zeid AlOthman3Claudiu T. Supuran4Università degli Studi di FirenzeUniversità degli Studi di FirenzeKing Saud UniversityKing Saud UniversityUniversità degli Studi di FirenzeA series of new derivatives was prepared by derivatisation of the 7-amino moiety present in 7-amino-3,4-dihydroquinolin-2(1H)-one, a compound investigated earlier as CAI. The derivatisation was achieved by: i) reaction with arylsulfonyl isocyanates/aryl isocyanates; (ii) reaction with fluorescein isothiocyanate; (iii) condensation with substituted benzoic acids in the presence of carbodiimides; (iv) reaction with 2,4,6-trimethyl-pyrylium tetrafluoroborate; (v) reaction with methylsulfonyl chloride and (vi) reaction with maleic anhydride. The new compounds were assayed as inhibitors of four carbonic anhydrases (CA, EC 4.2.1.1) human (h) isoforms of pharmacologic relevance, the cytosolic hCA I and II, the membrane-anchored hCA IV and the transmembrane, tumour-associated hCA IX. hCA IX was the most inhibited isoform (KIs ranging between 243.6 and 2785.6 nm) whereas hCA IV was not inhibited by these compounds. Most derivatives were weak hCA I and II inhibitors, with few of them showing KIs < 10 µm. Considering that the inhibition mechanism with these lactams is not yet elucidated, exploring a range of such derivatives with various substitution patterns may be useful to identify leads showing isoform selectivity or the desired pharmacologic action.http://dx.doi.org/10.1080/14756366.2017.1337759Carbonic anhydraseinhibitorcoumarindihydroquinolinonesulfonamide |
| spellingShingle | Murat Bozdag Silvia Bua Sameh M. Osman Zeid AlOthman Claudiu T. Supuran Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase inhibitor coumarin dihydroquinolinone sulfonamide |
| title | Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives |
| title_full | Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives |
| title_fullStr | Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives |
| title_full_unstemmed | Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives |
| title_short | Carbonic anhydrase I, II, IV and IX inhibition with a series of 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives |
| title_sort | carbonic anhydrase i ii iv and ix inhibition with a series of 7 amino 3 4 dihydroquinolin 2 1h one derivatives |
| topic | Carbonic anhydrase inhibitor coumarin dihydroquinolinone sulfonamide |
| url | http://dx.doi.org/10.1080/14756366.2017.1337759 |
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