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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Autores principales: Avula, Sreenivas, Peng, Xudan, Lang, Xingfen, Tortorella, Micky, Josselin, Béatrice, Bach, Stéphane, Bourg, Stephane, Bonnet, Pascal, Buron, Frédéric, Ruchaud, Sandrine, Routier, Sylvain, Neagoie, Cleopatra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
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Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186362/
https://www.ncbi.nlm.nih.gov/pubmed/35670091
http://dx.doi.org/10.1080/14756366.2022.2082419
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author Avula, Sreenivas
Peng, Xudan
Lang, Xingfen
Tortorella, Micky
Josselin, Béatrice
Bach, Stéphane
Bourg, Stephane
Bonnet, Pascal
Buron, Frédéric
Ruchaud, Sandrine
Routier, Sylvain
Neagoie, Cleopatra
author_facet Avula, Sreenivas
Peng, Xudan
Lang, Xingfen
Tortorella, Micky
Josselin, Béatrice
Bach, Stéphane
Bourg, Stephane
Bonnet, Pascal
Buron, Frédéric
Ruchaud, Sandrine
Routier, Sylvain
Neagoie, Cleopatra
author_sort Avula, Sreenivas
collection PubMed
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 IC(50) 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.
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spelling pubmed-91863622022-06-11 Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors Avula, Sreenivas Peng, Xudan Lang, Xingfen Tortorella, Micky Josselin, Béatrice Bach, Stéphane Bourg, Stephane Bonnet, Pascal Buron, Frédéric Ruchaud, Sandrine Routier, Sylvain Neagoie, Cleopatra J Enzyme Inhib Med Chem Original Article 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 IC(50) 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. Taylor & Francis 2022-06-07 /pmc/articles/PMC9186362/ /pubmed/35670091 http://dx.doi.org/10.1080/14756366.2022.2082419 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Avula, Sreenivas
Peng, Xudan
Lang, Xingfen
Tortorella, Micky
Josselin, Béatrice
Bach, Stéphane
Bourg, Stephane
Bonnet, Pascal
Buron, Frédéric
Ruchaud, Sandrine
Routier, Sylvain
Neagoie, Cleopatra
Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors
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 Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186362/
https://www.ncbi.nlm.nih.gov/pubmed/35670091
http://dx.doi.org/10.1080/14756366.2022.2082419
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