In silico, synthesis and anticancer evaluation of benzamide tryptamine derivatives as novel eEF2K inhibitors

Liu, Zedong; Jiang, Aili; Wang, Yaqi; Xu, Peng; Zhang, Qiting; Wang, Yinda; He, Shan; Wang, Ning; Jin, Haixiao; Zhang, Bin

doi:10.1016/j.bmcl.2022.128759

Cited by 8 publications

(2 citation statements)

References 28 publications

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“…Such modeling efforts with the crystal structure of MHCKA to predict the eEF2K catalytic domain protein structure was also used more recently to evaluate benzamide tryptamine derivatives as inhibitors [ 50 ]. This study used the approach of predicting druggability in silico prior to using an MTT assay to monitor proliferative effects, revealing a relationship between activity and placement of the indole or benzene ring, respectively [ 50 ].…”

Section: Structural Characterization Of Mhcka Advanced Eef2k Drug Dis...mentioning

confidence: 99%

eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design

Klupt

Jia

2023

Molecules

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The α-kinase, eEF2K, phosphorylates the threonine 56 residue of eEF2 to inhibit global peptide elongation (protein translation). As a master regulator of protein synthesis, in combination with its unique atypical kinase active site, investigations into the targeting of eEF2K represents a case of intense structure-based drug design that includes the use of modern computational techniques. The role of eEF2K is incredibly diverse and has been scrutinized in several different diseases including cancer and neurological disorders—with numerous studies inhibiting eEF2K as a potential treatment option, as described in this paper. Using available crystal structures of related α-kinases, particularly MHCKA, we report how homology modeling has been used to improve inhibitor design and efficacy. This review presents an overview of eEF2K related drug discovery efforts predating from the 1990’s, to more recent in vivo studies in rat models. We also provide the reader with a basic introduction to several approaches and software programs used to undertake such drug discovery campaigns. With the recent exciting publication of an eEF2K crystal structure, we present our view regarding the future of eEF2K drug discovery.

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Section: Structural Characterization Of Mhcka Advanced Eef2k Drug Dis...mentioning

confidence: 99%

eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design

Klupt

Jia

2023

Molecules

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“…[4] Targeted therapy is an important drug development strategy that is used in cancer patients. [8] Amide compounds, have been developed in the last few decades, act as key skeletons in many natural products and pharmacophores, as well as in precursors used in reactions. [9] These compounds exhibit biological activities such as antitumor, anti-HIV, neurological antagonists, antibiotic, antifungal and carbonic anhydrase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Nitro Compounds Inhibit Breast Cancer Cell Proliferation, Migration, and Colony Formation: Molecular Docking, Molecular Dynamics Simulations and Pharmacological Properties

Comert Onder,

Sahin,

Davutlar

et al. 2023

ChemistrySelect

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In this study, the concept of combined in vitro and in silico studies were utilized by using some synthesized nitro bearing compounds. The anticancer activities of the studied compounds were performed by using colony formation analysis, cell cytotoxicity, and migration. Nitro group containing two compounds were analyzed using Hoechst staining to indicate the morphological changes on the nuclei of cancer cells under fluorescence microscopy. Scanning electron microscopy (SEM) analysis was performed with N,N‐dibutyl‐nitro‐substituted compound. Nitro containing anticancer agents were shown the inhibition at 1.5 μM and 2 μM concentrations, and nuclear apoptosis was detected. In addition, cell‐to‐cell interaction on MDA‐MB‐231 cells was broken and observed morphologic changes following the treatment with N,N‐dibutyl‐nitro‐substituted compound at the effective doses. In general, the other nitro compounds showed cell cytotoxicity at 5 μM, 10 μM, and 20 μM. Two hits as anticancer agents were determined as potential interleukin‐1 receptor‐associated kinase 1 (IRAK1) and interleukin‐1 receptor‐associated kinase 4 (IRAK4) inhibitor candidates. Molecular docking and molecular dynamics (MD) simulations studies will provide that the binding patterns with specific residues such as Met265, Tyr284 of the IRAK family members, and these will contribute to further in vitro and in vivo studies for targeted breast cancer therapy.

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RETRACTED ARTICLE: Novel thiazole carbamothioyl benzamide derivative Mn(II), Ni(II), and Cu(II) complexes: synthesis, structural characterisation, computational, and biological potency

Al-Farraj,

El-Gamil,

Asla

2023

Opt Quant Electron

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In silico, synthesis and anticancer evaluation of benzamide tryptamine derivatives as novel eEF2K inhibitors

Cited by 8 publications

References 28 publications

eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design

eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design

Nitro Compounds Inhibit Breast Cancer Cell Proliferation, Migration, and Colony Formation: Molecular Docking, Molecular Dynamics Simulations and Pharmacological Properties

RETRACTED ARTICLE: Novel thiazole carbamothioyl benzamide derivative Mn(II), Ni(II), and Cu(II) complexes: synthesis, structural characterisation, computational, and biological potency

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