Design and biological evaluation of substituted 5,7-dihydro-6<i>H</i>-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors - Archive ouverte HAL Access content directly
Journal Articles Journal of Enzyme Inhibition and Medicinal Chemistry Year : 2022

Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors

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Abstract

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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Dates and versions

hal-03867334 , version 1 (23-11-2022)

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Attribution - CC BY 4.0

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Sreenivas Avula, Xudan Peng, Xingfen Lang, Micky Tortorella, Béatrice Josselin, et al.. 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, 2022, 37, pp.1632 - 1650. ⟨10.1080/14756366.2022.2082419⟩. ⟨hal-03867334⟩
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