Discovery and structure–activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents

Kwak, Seung-Hwa; Kang, Jung‐Ah; Kim, Minjeong; Lee, So‐Deok; Park, Jin Hee; Park, Sung‐Gyoo; Ko, Hyojin; Kim, Yong-Chul

doi:10.1016/j.bmc.2016.08.051

Cited by 6 publications

(1 citation statement)

References 34 publications

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“…In same year, Seung-Hwa Kwak and his group reported a detailed structure–activity relationship analysis of a series of novel quinolinone–carboxamide derivatives and their immunosuppressive effects on IL-2 released from activated T cells. After the optimization of the procedure, the results showed that the synthesized analogues could be used as lead compounds in the design and development of new immunosuppressant agents for treating T cell-mediated immune disorders, while one of them showed significant potency ( q1 ; Figure 3 ) [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone

Kostopoulou,

Tzani,

Chronaki

et al. 2023

Molecules

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In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone–carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.

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Section: Introductionmentioning

confidence: 99%