Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities
Novel quinazolinones conjugated with indole acetamide (4a–c), ibuprofen (7a–e), or thioacetohydrazide (13a,b, and 14a-d) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID...
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1956912 |
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doaj-3fdf57b999254bc881704aae6459b2902021-08-09T15:50:06ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-013611810182810.1080/14756366.2021.19569121956912Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activitiesAsmaa Sakr0Samar Rezq1Samy M. Ibrahim2Eman Soliman3Mohamed M. Baraka4Damian G. Romero5Hend Kothayer6Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig UniversityDepartment of Medicinal Chemistry, Faculty of Pharmacy, Zagazig UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig UniversityDepartment of Medicinal Chemistry, Faculty of Pharmacy, Zagazig UniversityDepartment of Cell and Molecular Biology, University of Mississippi Medical CenterDepartment of Medicinal Chemistry, Faculty of Pharmacy, Zagazig UniversityNovel quinazolinones conjugated with indole acetamide (4a–c), ibuprofen (7a–e), or thioacetohydrazide (13a,b, and 14a-d) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID analogue and had equipotent COX-2 selectivity as celecoxib. Compared with celecoxib, 4 b, 7c, and 13 b showed similar anti-inflammatory activity in vivo, while 13 b and 14a showed superior inhibition of the inflammatory mediator nitric oxide, and 7 showed greater antioxidant potential in macrophages cells. Moreover, all selected compounds showed improved analgesic activity and 13 b completely abolished the pain response. Additionally, compound 4a showed anticancer activity in tested cell lines HCT116, HT29, and HCA7. Docking results were consistent with COX-1/2 enzyme assay results. In silico studies suggest their high oral bioavailability. The overall findings for compounds (4a,b, 7c, 13 b, and 14c) support their potential role as anti-inflammatory agents.http://dx.doi.org/10.1080/14756366.2021.1956912cox-2 inhibitionquinazolinoneanti-inflammatorymolecular modellinganticancer |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Asmaa Sakr Samar Rezq Samy M. Ibrahim Eman Soliman Mohamed M. Baraka Damian G. Romero Hend Kothayer |
| spellingShingle |
Asmaa Sakr Samar Rezq Samy M. Ibrahim Eman Soliman Mohamed M. Baraka Damian G. Romero Hend Kothayer Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities Journal of Enzyme Inhibition and Medicinal Chemistry cox-2 inhibition quinazolinone anti-inflammatory molecular modelling anticancer |
| author_facet |
Asmaa Sakr Samar Rezq Samy M. Ibrahim Eman Soliman Mohamed M. Baraka Damian G. Romero Hend Kothayer |
| author_sort |
Asmaa Sakr |
| title |
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| title_short |
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| title_full |
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| title_fullStr |
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| title_full_unstemmed |
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| title_sort |
design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective cox-2 inhibitors: anti-inflammatory, analgesic and anticancer activities |
| publisher |
Taylor & Francis Group |
| series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
| issn |
1475-6366 1475-6374 |
| publishDate |
2021-01-01 |
| description |
Novel quinazolinones conjugated with indole acetamide (4a–c), ibuprofen (7a–e), or thioacetohydrazide (13a,b, and 14a-d) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID analogue and had equipotent COX-2 selectivity as celecoxib. Compared with celecoxib, 4 b, 7c, and 13 b showed similar anti-inflammatory activity in vivo, while 13 b and 14a showed superior inhibition of the inflammatory mediator nitric oxide, and 7 showed greater antioxidant potential in macrophages cells. Moreover, all selected compounds showed improved analgesic activity and 13 b completely abolished the pain response. Additionally, compound 4a showed anticancer activity in tested cell lines HCT116, HT29, and HCA7. Docking results were consistent with COX-1/2 enzyme assay results. In silico studies suggest their high oral bioavailability. The overall findings for compounds (4a,b, 7c, 13 b, and 14c) support their potential role as anti-inflammatory agents. |
| topic |
cox-2 inhibition quinazolinone anti-inflammatory molecular modelling anticancer |
| url |
http://dx.doi.org/10.1080/14756366.2021.1956912 |
| work_keys_str_mv |
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