Synthesis, anticancer activity and mechanism of iron chelator derived from 2,6-diacetylpyridine bis(acylhydrazones)

Yao, Qian; Qi, Jinxu; Zheng, Yunyun; Qian, Kun; Wei, Lai; Maimaitiyiming, Mukedasi; Cheng, Zhen; Wang, Yihong

doi:10.1016/j.jinorgbio.2019.01.003

Cited by 10 publications

(7 citation statements)

References 56 publications

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“…The metal chelator binding to iron in the R2 subunit would inhibit the activity of RR and subsequent cell proliferation [43]. Previous research also demonstrated that acylhydrazones exhibited anticancer proliferation activity through their iron chelating effects [43], which was consistent with our finding.…”

Section: Discussionsupporting

confidence: 91%

“…RR catalyzes the production of a stable lysyl radical by combining the oxygen with the Fe-O-Fe structure in the R2 subunit and serves as a key enzyme for DNA synthesis and repair. The metal chelator binding to iron in the R2 subunit would inhibit the activity of RR and subsequent cell proliferation [43]. Previous research also demonstrated that acylhydrazones exhibited anticancer proliferation activity through their iron chelating effects [43], which was consistent with our finding.…”

Section: Discussionsupporting

confidence: 91%

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Synthesis and Evaluation of Pyridoxal Hydrazone and Acylhydrazone Compounds as Potential Angiogenesis Inhibitors

Chen

Liu

et al. 2019

Pharmacology

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Background/Aims: Hydrazone and acylhydrazone derivatives, which are produced from aldehyde reacting with hydrazine or acylhydrazine, have been reported to exhibit antitumor activities. However, the angionenic effects of this kind of derivatives haven’t been elucidated. Here, we synthesized 12 pyridoxal hydrazone and acylhydrazone compounds and investigated their antiangiogenic effects and the underlying mechanisms. Method: 3-(4,5-Dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide assay was used to screen the inhibitory effects of the synthesized compounds on endothelial cells (ECs) proliferation. The compound with best inhibitory effect was further evaluated with wound-healing assay and tube formation assay. Calcein-Am assay was carried out to determine the content of intracellular labile iron pool (LIP). Intracellular reduced glutathione (GSH) was determined by spectrophotometry. Flow cytometry was used to determine cell cycle and apoptosis. Results: Compound 10 (3-hydroxy-5-[hydroxymethyl]-2-methyl-pyridine-4-carbaldehyde-2-naphthalen-1-acetyl hydrazone) showed the best inhibitory effect on human umbilical vascular ECs proliferation, with IC50 value of 25.4 μmol/L. It not only inhibited wound-healing and tube formation of ECs, but also decreased the content of intracellular LIP and GSH. Furthermore, it arrested ECs cycle at S phase and induced cell apoptosis. Conclusions: Compound 10 exhibits antiangiogenic effects by reducing the content of intracellular LIP and GSH, and subsequently arresting cell cycle and inducing cell apoptosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Synthesis and Evaluation of Pyridoxal Hydrazone and Acylhydrazone Compounds as Potential Angiogenesis Inhibitors

Chen

Liu

et al. 2019

Pharmacology

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“…In leukemic cells (HL-60) it was observed that only the compound VAN-2 did not present cytotoxic activity, and the derivatives of cinnamaldehyde CIN-1 and CIN-2 are the most active hybrids in front of this cellular lineage, with GI of 92.37 ± 3.60% and 89.62 ± 3.54%, respectively. CIN-2 hydrazone is the only acylhydrazone in the tested series, and was obtained through molecular hybridization between cinnamaldehyde and isoniazid, and the latter is a drug used clinically in the treatment of tuberculosis [18].…”

Section: Resultsmentioning

confidence: 99%

Hydrazones derived from natural aldehydes: in vitro cytotoxic evaluation and in silico pharmacokinetic predictions

Araújo

Santos

Gonsalves

et al. 2021

Rev. Colomb. Cienc. Quím. Farm.

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Introduction: Recent research has reported the cytotoxic potential of hydrazones against various strains of cancer cells. Aim: To evaluate the anticancer activity in vitro and the pharmacokinetic profile of six synthesized hydrazonic compounds, identified as vanillin 1-phthalazinylhydrazone (VAN-1); 2,4-dinitrophenylhydrazone vanillin (VAN-2); phenylhydrazone cinnamaldehyde (CIN-1); isonicotinoyl hydrazone cinnamaldehyde (CIN-2); cinnamaldehyde 1 phthalazinylhydrazone (CIN-3); and 2,4 dinitrophenylhydrazone cinnamaldehyde (CIN-4). Thecytotoxic activity was evaluated against four strains of cancer cells. Methodology: Thepharmacokinetic parameters of absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of the hydrazones were evaluated using the PreADMET program. Results: Hydrazones derived from cinnamaldehyde (CIN-1 and CIN-2) showed high cytotoxic activity against leukemic (HL-60) and glioblastomas (SF-295) cell lines. The pharmacokinetic profile of the hydrazones showed that, in general, the hydrazones presented satisfactory characteristics of ADME/T. In addition, it was observed that CIN-2 presented the most promising in silico profile, showing high intestinal absorption, desirable distribution profile related to plasma protein binding, adequate renal excretion, and low toxicity. The ADME/T profile of the CIN-1 compound highlighted its potential as a promising antineoplastic agent with action of the CNS, more specifically against glioblastomas.

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“…Acylhydrazones have significant importance in the pharmaceutical field through numerous biological properties with multiple therapeutic indications. In the research studies performed using compounds from the acylhydrazone class, the following actions were reported: antitumor [25][26][27][28][39][40][41] and [42][43][44][45][46][47][48][49][50][51], cytotoxic [52], antibacterial [4,12,31,33-35] [53-59], antifungal [34,60,61], antiviral [62][63][64][65][66][67][68][69], antiparasitic [6,45,[70][71][72][73][74][75][76], anti-inflammatory [32,73,[77][78][79][80][81][82][83]…”

Section: Biological Propertiesmentioning

confidence: 99%

Acylhydrazones and Their Biological Activity: A Review

et al. 2022

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Due to the structure of acylhydrazones both by the pharmacophore –CO–NH–N= group and by the different substituents present in the molecules of compounds of this class, various pharmacological activities were reported, including antitumor, antimicrobial, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, antiedematous, antiglaucomatous, antidiabetic, antioxidant, and actions on the central nervous system and on the cardiovascular system. This fragment is found in the structure of several drugs used in the therapy of some diseases that are at the top of public health problems, like microbial infections and cardiovascular diseases. Moreover, the acylhydrazone moiety is present in the structure of some compounds with possible applications in the treatment of other different pathologies, such as schizophrenia, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Considering these aspects, we consider that a study of the literature data regarding the structural and biological properties of these compounds is useful.

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Synthesis, anticancer activity and mechanism of iron chelator derived from 2,6-diacetylpyridine bis(acylhydrazones)

Cited by 10 publications

References 56 publications

Synthesis and Evaluation of Pyridoxal Hydrazone and Acylhydrazone Compounds as Potential Angiogenesis Inhibitors

Synthesis and Evaluation of Pyridoxal Hydrazone and Acylhydrazone Compounds as Potential Angiogenesis Inhibitors

Hydrazones derived from natural aldehydes: in vitro cytotoxic evaluation and in silico pharmacokinetic predictions

Acylhydrazones and Their Biological Activity: A Review

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