Design, synthesis and biological evaluation of hydantoin derivatives as Mcl-1 selective inhibitors

Liang, Xiao; Li, Xue; Zhao, Zhiyuan; Nie, Yiming; Yao, Zefu; Ren, Wandi; Xia, Yang; Hou, Xuben; Fang, Hao

doi:10.1016/j.bioorg.2022.105643

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…The synthetic feasibility for core scaffolds and the ease of accepting various substituents are the two main attractive characteristics of hydantoins 11 . Previous studies have reported that 3‐aminohydontoin or 3‐aminoimidazilidin‐2,4‐dione moiety presents a versatile scaffold that exerts a wide range of biological and pharmacological activities, which may be related to neurodegenerative diseases, such as anti‐apoptotic, antioxidant, anti‐inflammatory and modulator of N‐formyl peptide receptor like‐1 (FPRL‐1) 11–17 …”

Section: Introductionmentioning

confidence: 99%

“…11 Previous studies have reported that 3-aminohydontoin or 3-aminoimidazilidin-2,4-dione moiety presents a versatile scaffold that exerts a wide range of biological and pharmacological activities, which may be related to neurodegenerative diseases, such as antiapoptotic, antioxidant, anti-inflammatory and modulator of N-formyl peptide receptor like-1 (FPRL-1). [11][12][13][14][15][16][17] To our knowledge, the properties of the 3-aminohydantoin derivatives have not yet been evaluated thoroughly in a chronic degenerative context. Our study is the first to investigate the efficacy of 3-aminoimidazilidin-2,4-dione moiety in treating Parkinson's disease.…”

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confidence: 99%

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3‐aminohydantoin derivate as a promising scaffold in dopaminergic neuroprotection and neurorescue in the in vivo and in vitro 6‐hydroxydopamine models of Parkinson's disease

Mani,

Bouchnak,

Pradeloux

et al. 2023

Clin Exp Pharma Physio

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra, for which no disease‐modifying treatments are available yet. Thus, developing new neuroprotective drugs with the potential to delay or stop the natural course of the disease is necessary. The aim of the present study was to evaluate the neuroprotective effects of a newly synthesized 3‐aminohydantoin derivative named 3‐amino‐5‐benzylimidazolidine‐2,4‐dione (PHAH). The possible neuroprotective and neurorescue effects of the synthesized compound were tested: (i) in N27 dopaminergic and BV‐2 microglial cell lines treated with 6‐hydroxydopamine (6‐OHDA) and (ii) in the 6‐OHDA rat model of PD. PHAH administration reduced proinflammatory markers, including nitric oxide synthase and interleukin‐1β, in BV‐2 cells activated by lipopolysaccharide. Although PHAH did not restore cell death induced by 6‐OHDA, it was not cytotoxic for dopaminergic cells since cell viability, under the effect of the two concentrations, remained comparable to that of the control cells. Most interestingly, PHAH restored 6‐OHDA‐induced dopaminergic neurodegeneration in the substantia nigra and striatum and ameliorated 6‐OHDA‐induced oxidative stress in the rat brain. In summary, we have proven that in PD models, PHAH has neuroprotective effects in vivo and anti‐inflammatory effects in vitro; however, these effects remain to be confirmed by carrying out certain specific behavioural tests as well as by exploring other neuroinflammatory markers. The present work also suggests that PHAH is a promising scaffold that can serve as the basis for the design and synthesis of other derivatives that can be potent antiparkinsonian agents.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

3‐aminohydantoin derivate as a promising scaffold in dopaminergic neuroprotection and neurorescue in the in vivo and in vitro 6‐hydroxydopamine models of Parkinson's disease

Mani,

Bouchnak,

Pradeloux

et al. 2023

Clin Exp Pharma Physio

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“…Hydantoin (systematically imidazolidine-2,4-dione) represents a structural motif that has been of interest to many researchers in recent years, not only chemically but also biologically [ 24 , 25 , 26 , 27 ]. Hydantoin-based compounds exhibit a broad range of biological activities, such as fungicidal, herbicidal, antitumor, anti-inflammatory, anti-HIV, hypolipidemic, antiarrhythmic, antiplatelet, and antihypertensive activities [ 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Rearrangement of Pyrazino[2,3-c]quinolin-5(6H)-ones during Their Reaction with Isocyanic Acid

Klásek

Lyčka

Křemen

et al. 2022

IJMS

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New tetrahydropyrazino[2,3-c]quinolin-5(6H)-ones were prepared from 3-chloroquinoline-2,4(1H,3H)-diones and ethylene diamine. In their reaction with HNCO, an unprecedented molecular rearrangement produced new types of hydantoin derivatives. All prepared compounds were characterized on the basis of their 1H, 13C, and 15N NMR and ESI mass spectra and some were authenticated by X-ray analysis of single crystalline material. A proposed mechanism for rearrangement is discussed in this essay. The CDK and ABL inhibition activity as well as in vitro cytotoxicity of the prepared compounds was also tested.

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Development of a series of novel Mcl-1 inhibitors bearing an indole carboxylic acid moiety

Deng

Huang

Liu

et al. 2022

Bioorganic Chemistry

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Design, synthesis and biological evaluation of hydantoin derivatives as Mcl-1 selective inhibitors

Cited by 4 publications

References 22 publications

3‐aminohydantoin derivate as a promising scaffold in dopaminergic neuroprotection and neurorescue in the in vivo and in vitro 6‐hydroxydopamine models of Parkinson's disease

3‐aminohydantoin derivate as a promising scaffold in dopaminergic neuroprotection and neurorescue in the in vivo and in vitro 6‐hydroxydopamine models of Parkinson's disease

Molecular Rearrangement of Pyrazino[2,3-c]quinolin-5(6H)-ones during Their Reaction with Isocyanic Acid

Development of a series of novel Mcl-1 inhibitors bearing an indole carboxylic acid moiety

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