Synthesis and biological evaluations of N′-substituted methylene-4-(quinoline-4-amino) benzoylhydrazides as potential anti-hepatoma agents

Li, Baicun; Zhu, Fengsen; He, Fengming; Huang, Qingqing; Liu, Xiaoguang; Wu, Tong; Zhao, Taige; Qiu, Ying-Kun; Wu, Zhixian; Xue, Yuhua; Fang, Meijuan

doi:10.1016/j.bioorg.2020.103592

Cited by 16 publications

(5 citation statements)

References 22 publications

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“…Standard procedures were applied to remove solvents and dry products. Instrumentation employed in compound synthesis and structural characterisation, such as Nuclear Magnetic Resonance Spectroscopy, Mass Spectrograph, High Performance Liquid Chromatography, and microscope melting point apparatus, was in accordance with our prior publications 18 , 33 .…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma

Chen

Zhao

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Nur77 modulators have emerged as a promising therapeutic approach for hepatocellular carcinoma. In this study, a structure-based rational drug design approach was used to design and synthesise a series of 4-((8-hydroxy-2-methylquinolin-4-yl)amino)benzoylhydrazone derivatives based on the binding characteristics of our previously reported 10g and the native ligand 3NB at the binding Site C of Nur77. Cell-based cytotoxicity assays revealed that compound TMHA37 demonstrated the highest cytotoxicity against all tested cancer cells. The induced fit docking and binding pose metadynamics simulation suggested that TMHA37 was the most promising Nur77 binder at Site C. Molecular dynamics simulation validated the stable binding of TMHA37 to Nur77’s Site C but not to Sites A or B. Specifically, TMHA37 bound strongly to Nur77-LBD ( K D = 445.3 nM) and could activate Nur77’s transcriptional activity. Furthermore, TMHA37 exhibited antitumor effects by blocking the cell cycle at G2/M phase and inducing cell apoptosis in a Nur77-dependent manner.

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Section: Methodsmentioning

confidence: 99%

Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma

Chen

Zhao

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Aromatic heterocycles were not helpful for the cytotoxic action when added at the N '‐methylene. [ 87 ]…”

Section: N‐acylhydrazones As Anticancer Agentsmentioning

confidence: 99%

“…Aromatic heterocycles were not helpful for the cytotoxic action when added at the N'-methylene. [87] A very promising strategy for treating cancer is to target A molecule with nanomolar potency was produced by adding a 3-hydroxy group to the phenyl ring. The phenolic oxygen was alkylated, which reduced PI3Kα activity.…”

Section: N-acylhydrazones As Antiangiogenesis Agentsmentioning

confidence: 99%

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Kassab

2023

Archiv der Pharmazie

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The N-acylhydrazone motif has been shown to be particularly adaptable and promising in the area of medicinal chemistry and drug development, due to its significant biological and pharmacological characteristics. Moreover, N-acylhydrazones are appealing synthetic and biological tools because of their simple and straightforward synthesis. This scaffold has emerged as a fundamental building block for the synthesis of bioactive compounds.Particularly, the N-acylhydrazone scaffold served as a base for the synthesis of a number of potent anticancer agents acting via different mechanisms. An updated summary of the anticancer activity of N-acylhydrazone derivatives described in the literature (from 2017 to 2022) is provided in the current review. It discusses the structure-activity relationship (SAR) of N-acylhydrazone derivatives exhibiting anticancer potential, which could be helpful in designing and developing new derivatives as effective antiproliferative candidates in the future.

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“…Kardile et al reported the in vitro screening, molecular docking, and absorption, distribution, metabolism, and excretion (ADME) predictions of quinolone derivatives . The derivatives with a quinoline core are also known as potent tubulin assembly inhibitors, mutant epidermal growth factor receptor (EGFR) inhibitors targeting resistance in lung cancer cells, anti-tubulin agents targeting the colchicine binding site, potential anti-hepatoma agents, and various other anticancer activities; − hence, we intend to synthesize new quinoline derivatives and screen them for their activity against the breast cancer 3ERT protein. The synthesis of biaryls involving carbon–carbon bond formation through palladium-mediated Suzuki–Miyaura cross-coupling plays a key role in the synthetic chemistry to build complex molecules from simple precursors since the formation of biaryls using Suzuki–Miyaura coupling is the most reliable and efficient method .…”

Section: Introductionmentioning

confidence: 99%

Palladium-Mediated Synthesis of 2-([Biphenyl]-4-yloxy)quinolin-3-carbaldehydes through Suzuki–Miyaura Cross-Coupling and Their in Silico Breast Cancer Studies on the 3ERT Protein

et al. 2023

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A series of novel quinoline appended biaryls have been synthesized (5a−5o) by reacting various substituted boronic acids (4e−4h) with various substituted 2-(4-bromophenoxy)quinolin-3-carbaldehydes (3a−3d) through carbon−carbon bond formation. Effects of various quinoline appended biaryls (5a−5o) on the breast cancer protein 3ERT are moderate to high, as found by in silico molecular docking studies. Comparatively, all quinoline appended biaryls (5a−5o) 5h show better efficacy with a binding energy of −9.39 kcal/mol, and hydrogen bonds are Thr347, Glu353, and Arg394 in the binding pocket. Conclusively, the final novel quinoline appended biaryls (5a−5o) have been confirmed with all the spectral studies, and their efficacy has been validated with in silico studies.

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Synthesis and biological evaluations of N′-substituted methylene-4-(quinoline-4-amino) benzoylhydrazides as potential anti-hepatoma agents

Cited by 16 publications

References 22 publications

Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma

Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Palladium-Mediated Synthesis of 2-([Biphenyl]-4-yloxy)quinolin-3-carbaldehydes through Suzuki–Miyaura Cross-Coupling and Their in Silico Breast Cancer Studies on the 3ERT Protein

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