Design, synthesis, and biological evaluation of imidazoline derivatives as p53–MDM2 binding inhibitors

Hu, Chunqi; Li, Xin; Wang, Weisi; Zhang, Lei; Tao, Lulu; Dong, Xiaowu; Sheng, Rong; Yang, Bo; Hu, Yongzhou

doi:10.1016/j.bmc.2011.07.050

Cited by 20 publications

(18 citation statements)

References 16 publications

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“…Moreover, Bonilla-Ramirez et al, [132] have found that desferrioxamine (DFO), ethylenediaminetetraacetic acid (EGTA), and D-penicillamine chelators were able to protect but not rescue D. melanogaster against acute or chronic metal intoxication. Taken together, in vitro and in vivo data suggest that antioxidants (e.g., NAC [133]), polyphenols, cannabinoids, metal chelators [134], mitochondrial targeted antioxidant compounds [135, 136], pharmacological inhibition of NF- κ B [137, 138], p53 [139, 140], JNK [141], and caspase-3 may be of therapeutic value in AD and PD.…”

Section: The Bad Touch Of Oxidative Stress: Involvement In Alzheimmentioning

confidence: 99%

The Bad, the Good, and the Ugly about Oxidative Stress

Jiménez-Del-Río

Vélez-Pardo

2012

Oxidative Medicine and Cellular Longevity

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Alzheimer's disease (AD), Parkinson's disease (PD), and cancer (e.g., leukemia) are the most devastating disorders affecting millions of people worldwide. Except for some kind of cancers, no effective and/or definitive therapeutic treatment aimed to reduce or to retard the clinic and pathologic symptoms induced by AD and PD is presently available. Therefore, it is urgently needed to understand the molecular basis of these disorders. Since oxidative stress (OS) is an important etiologic factor of the pathologic process of AD, PD, and cancer, understanding how intracellular signaling pathways respond to OS will have a significant implication in the therapy of these diseases. Here, we propose a model of minimal completeness of cell death signaling induced by OS as a mechanistic explanation of neuronal and cancer cell demise. This mechanism might provide the basis for therapeutic design strategies. Finally, we will attempt to associate PD, cancer, and OS. This paper critically analyzes the evidence that support the “oxidative stress model” in neurodegeneration and cancer.

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Section: The Bad Touch Of Oxidative Stress: Involvement In Alzheimmentioning

confidence: 99%

The Bad, the Good, and the Ugly about Oxidative Stress

Jiménez-Del-Río

Vélez-Pardo

2012

Oxidative Medicine and Cellular Longevity

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“…The structures of all the synthesized compounds were confirmed by IR, 1 H NMR and mass spectral data. Table 1 shows the physical parameters of synthesized imidazoline compounds.…”

Section: Methodsmentioning

confidence: 67%

“…The synthesis of imidazoline derivatives continues to attract much interest in organic chemistry due to its various therapeutic properties [1][2][3][4][5][6][7][8]. This class of compounds is known to have applications in various fields [9,10].…”

Section: Introductionmentioning

confidence: 99%

Physicochemical Study of some Imidazoline Derivatives in Solutions

Baluja

Kacchadia

2015

ILCPA

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“…2) [229,[297][298][299], were identified via HTS. Structure-based design and molecular modeling were then used for ligand screening and optimization [300][301][302][303][304] leading to in vitro activities down to IC 50 = 3 nM [302]. Several computational techniques have helped designing and screening for ligands of HDM2 or MDM2.…”

Section: Hdm2mentioning

confidence: 99%

Modulating Protein-Protein Interactions: From Structural Determinants of Binding to Druggability Prediction to Application

Metz¹,

Ciglia²,

Gohlke³

2012

CPD

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During the last decades, a large amount of evidence has been gathered on the importance of protein-protein interactions in tuning and regulating most important biological processes. Since many of these pathways are deeply involved in diseases, extensive research efforts have been undertaken towards the modulation of protein-protein interactions. At the early stage of this challenge most of the attention was drawn to the drawbacks of such a therapeutic approach. Encouragingly, however, several recent studies provided a proof of concept that protein-protein interactions are actually valuable targets and that they do have a promising therapeutic potential. This review is divided into three sections. In the first section we summarize the general features of protein-protein interfaces, focusing on the characteristics that make them different from classical protein-ligand binding sites, as well as on problematic aspects that hamper the application of classical drug discovery approaches. In the second section, we present how some of the characteristics of protein-protein interactions can be exploited fruitfully in drug design, hence focusing on the druggability of protein-protein interfaces. Methods successfully applied to protein-protein interactions will be introduced, giving special attention to the computational ones. In the third section, three case studies are presented. First, we describe protein-protein interaction modulators targeting HDM2 and the computational methods applied to identify them. Next, we present the retrospective application of the discussed approaches on the well-examined target IL-2. We conclude with a prospective application to the NHR2 protein, a target just recently validated experimentally with the aid of computational methods.

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Design, synthesis, and biological evaluation of imidazoline derivatives as p53–MDM2 binding inhibitors

Cited by 20 publications

References 16 publications

The Bad, the Good, and the Ugly about Oxidative Stress

The Bad, the Good, and the Ugly about Oxidative Stress

Physicochemical Study of some Imidazoline Derivatives in Solutions

Modulating Protein-Protein Interactions: From Structural Determinants of Binding to Druggability Prediction to Application

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