Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues

Xie, Jizhao; Xu, Huanji; Wu, Xinduo; Xie, Yunfei; Lu, Xiuhong; Wang, Lisheng

doi:10.1016/j.bmcl.2021.128444

Cited by 11 publications

(7 citation statements)

References 26 publications

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“…Moreover, the mechanism of binding of compound 3 with RAGE remains ambiguous as no structural data are available to establish their binding modes and locations. However, molecular docking studies performed by Xie et al provide some basic notions of its binding mode with RAGE V‐domain (Xie et al, 2021) and they used this information to further design novel RAGE inhibitors by modifying the central structural moiety of azeliragon i.e., imidazole to triazole. They synthesized the designed compounds and tested them to check their anticancer potential against triple‐negative breast cancer cell line (TNBC) which is the most aggressive breast cancer cell line.…”

Section: Rage Inhibitorsmentioning

confidence: 99%

“…They synthesized the designed compounds and tested them to check their anticancer potential against triple‐negative breast cancer cell line (TNBC) which is the most aggressive breast cancer cell line. Amongst all the compounds, compound 4 was found to be endowed with the best inhibitory potential against TNBC cells with the IC 50 value of 0.220 µM (Xie et al, 2021) (Figure 3).…”

Section: Rage Inhibitorsmentioning

confidence: 99%

“…They synthesized the designed compounds and tested them to check their anticancer potential against triple-negative breast cancer cell line (TNBC) which is the most aggressive breast cancer cell line. Amongst all the compounds, compound 4 was found to be endowed with the best inhibitory potential against TNBC cells with the IC 50 value of 0.220 µM(Xie et al, 2021) (Figure3).Tranilast (compound 5) is an anti-allergic drug molecule that significantly inhibits the binding interactions of V-domain of RAGE with S100A11 and S100A12 which was tested using proton and nitrogen NMR titrations, fluorescence experiments, and WST-1 assay(Chiou et al, 2016;Huang et al, 2016) (Figure3). Different interacting amino acids present in the active domain (V-domain) of RAGE with tranilast were also revealed using high ambiguity-driven biomolecular docking (HADDOCK).…”

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confidence: 99%

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Therapeutic potential of targeting the receptor for advanced glycation end products (RAGE) by small molecule inhibitors

Singh

Agrawal

2022

Drug Development Research

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Receptor for advanced glycation end products (RAGE) is a 45 kDa transmembrane receptor of immunoglobulin family that can bind to various endogenous and exogenous ligands and initiate the inflammatory downstream signaling pathways. RAGE is involved in various disorders including cardiovascular and neurodegenerative diseases, cancer, and diabetes. This review summarizes the structural features of RAGE and its various isoforms along with their pathological effects.Mainly, the article emphasized on the translational significance of antagonizing the interactions of RAGE with its ligands using small molecules reported in the last 5 years and discusses future approaches that could be employed to block the interactions in the treatment of chronic inflammatory ailments. The RAGE inhibitors described in this article could prove as a powerful approach in the management of immune-inflammatory diseases. A critical review of the literature suggests that there is a dire need to dive deeper into the molecular mechanism of action to resolve critical issues that must be addressed to understand RAGE-targeting therapy and long-term blockade of RAGE in human diseases.

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Section: Rage Inhibitorsmentioning

confidence: 99%

Section: Rage Inhibitorsmentioning

confidence: 99%

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confidence: 99%

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Therapeutic potential of targeting the receptor for advanced glycation end products (RAGE) by small molecule inhibitors

Singh

Agrawal

2022

Drug Development Research

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“…Phase II clinical trial data of Azeliragon proved that it could delay the time period to cognitive deterioration in mild AD patients (Burstein et al, 2016(Burstein et al, , 2018. Unfortunately, owing to the toxicity, the dosage in phase III clinical trial was limited to 5 mg/day without obtaining any expected results (Xie et al, 2021).…”

Section: Preventing Aβ Aggregationmentioning

confidence: 99%

Small-molecule drugs development for Alzheimer's disease

Yao¹,

Yang²

2022

Front. Aging Neurosci.

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Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder with no effective therapeutic drugs currently. The complicated pathophysiology of AD is not well understood, although beta-amyloid (Aβ) cascade and hyperphosphorylated tau protein were regarded as the two main causes of AD. Other mechanisms, such as oxidative stress, deficiency of central cholinergic neurotransmitters, mitochondrial dysfunction, and inflammation, were also proposed and studied as targets in AD. This review aims to summarize the small-molecule drugs that were developed based on the pathogenesis and gives a deeper understanding of the AD. We hope that it could help scientists find new and better treatments to gradually conquer the problems related to AD in future.

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“…26 Among those, Azeliragon triazole analogues have recently been identified for their excellent activities. 27 Due to the triazole's high coordination affinity towards several transition metals, it was envisaged that the systematic investigation of relevant coordination complexes may open up new avenues and even more possibilities for the design and development of enhanced and more reliable anticancer agents. 28–31…”

Section: Introductionmentioning

confidence: 99%