Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors
A library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activit...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2082419 |
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| _version_ | 1850115021386809344 |
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| author | Sreenivas Avula Xudan Peng Xingfen Lang Micky Tortorella Béatrice Josselin Stéphane Bach Stephane Bourg Pascal Bonnet Frédéric Buron Sandrine Ruchaud Sylvain Routier Cleopatra Neagoie |
| author_facet | Sreenivas Avula Xudan Peng Xingfen Lang Micky Tortorella Béatrice Josselin Stéphane Bach Stephane Bourg Pascal Bonnet Frédéric Buron Sandrine Ruchaud Sylvain Routier Cleopatra Neagoie |
| author_sort | Sreenivas Avula |
| collection | DOAJ |
| description | A library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activity of the 22 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC50 of 1 and 2 nM with selectivity towards a panel of 10 other kinases including the parent kinases DYRK1A and CLK1. The most selective compound exerted additionally a very interesting cell effect on the osteosarcoma U-2 OS cell line. |
| format | Article |
| id | doaj-art-eae579ca70af4ec7902f09b889e08fbc |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-eae579ca70af4ec7902f09b889e08fbc2025-08-20T02:36:41ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711632165010.1080/14756366.2022.2082419Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitorsSreenivas Avula0Xudan Peng1Xingfen Lang2Micky Tortorella3Béatrice Josselin4Stéphane Bach5Stephane Bourg6Pascal Bonnet7Frédéric Buron8Sandrine Ruchaud9Sylvain Routier10Cleopatra Neagoie11Guangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou, ChinaGuangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou, ChinaGuangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou, ChinaGuangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou, ChinaSorbonne Université/CNRS UMR8227, Roscoff cedex, FranceSorbonne Université/CNRS UMR8227, Roscoff cedex, FranceInstitut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 7311, Orleans, FranceInstitut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 7311, Orleans, FranceInstitut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 7311, Orleans, FranceSorbonne Université/CNRS UMR8227, Roscoff cedex, FranceInstitut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 7311, Orleans, FranceGuangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou, ChinaA library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activity of the 22 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC50 of 1 and 2 nM with selectivity towards a panel of 10 other kinases including the parent kinases DYRK1A and CLK1. The most selective compound exerted additionally a very interesting cell effect on the osteosarcoma U-2 OS cell line.https://www.tandfonline.com/doi/10.1080/14756366.2022.2082419IndoloquinolineHaspin kinasedockingcell viability |
| spellingShingle | Sreenivas Avula Xudan Peng Xingfen Lang Micky Tortorella Béatrice Josselin Stéphane Bach Stephane Bourg Pascal Bonnet Frédéric Buron Sandrine Ruchaud Sylvain Routier Cleopatra Neagoie Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Indoloquinoline Haspin kinase docking cell viability |
| title | Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors |
| title_full | Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors |
| title_fullStr | Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors |
| title_full_unstemmed | Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors |
| title_short | Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors |
| title_sort | design and biological evaluation of substituted 5 7 dihydro 6h indolo 2 3 c quinolin 6 one as novel selective haspin inhibitors |
| topic | Indoloquinoline Haspin kinase docking cell viability |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2082419 |
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