Synthesis, characterization, and bioactivity of new bisamidrazone derivatives as possible anticancer agents

Al-Qtaitat, Malath A.; El‐Abadelah, Mustafa M.; Sabbah, Dima A.; Bardaweel, Sanaa K.; Sweidan, Kamal; Sabri, Salim S.; Mubarak, Mohammad S.

doi:10.1007/s00044-018-2158-0

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…Carboxamidrazones structurally resemble thiosemicarbazones, but, surprisingly, their anticancer effects were not extensively studied. These compounds demonstrated antiproliferative activity in the micromolar range and good selectivity to cancer cells over healthy cells [ 29 , 30 ]. Similarly to Cu(II)-TSC complexes, coordination of carboxamidrazones to Cu(II) improved the cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells

et al. 2020

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Thiosemicarbazones continue to attract the interest of researchers as potential anticancer drugs. For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or triapine, is the most well-known representative of this class of compounds that has entered multiple phase I and II clinical trials. Two new triapine derivatives HL1 and HL2 were prepared by condensation reactions of 2-pyridinamidrazone and S-methylisothiosemicarbazidium chloride with 3-N-(tert-butyloxycarbonyl) amino-pyridine-2-carboxaldehyde, followed by a Boc-deprotection procedure. Subsequent reaction of HL1 and HL2 with CuCl2·2H2O in 1:1 molar ratio in methanol produced the complexes [CuII(HL1)Cl2]·H2O (1·H2O) and [CuII(HL2)Cl2] (2). The reaction of HL2 with Fe(NO3)3∙9H2O in 2:1 molar ratio in the presence of triethylamine afforded the complex [FeIII(L2)2]NO3∙0.75H2O (3∙0.75H2O), in which the isothiosemicarbazone acts as a tridentate monoanionic ligand. The crystal structures of HL1, HL2 and metal complexes 1 and 2 were determined by single crystal X-ray diffraction. The UV-Vis and EPR spectroelectrochemical measurements revealed that complexes 1 and 2 underwent irreversible reduction of Cu(II) with subsequent ligand release, while 3 showed an almost reversible electrochemical reduction in dimethyl sulfoxide (DMSO). Aqueous solution behaviour of HL1 and 1, as well as of HL2 and its complex 2, was monitored as well. Complexes 1−3 were tested against ovarian carcinoma cells, as well as noncancerous embryonic kidney cells, in comparison to respective free ligands, triapine and cisplatin. While the free ligands HL1 and HL2 were devoid of antiproliferative activity, their respective metal complexes showed remarkable antiproliferative activity in a micromolar concentration range. The activity was not related to the inhibition of ribonucleotide reductase (RNR) R2 protein, but rather to cancer cell homeostasis disturbance—leading to the disruption of cancer cell signalling.

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Section: Introductionmentioning

confidence: 99%

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells

et al. 2020

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“…Molecular docking revealed a similarity of compounds 72 – 76 with imatinib (a drug belonging to the group of tyrosine kinase inhibitors) during interactions with bcr-abl tyrosine kinase, which may indicate a similar mechanism of action of those compounds [ 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. Alternatively, according to in silico studies, derivative 79 could act as an effective inhibitor of phosphatidylinositol 3-kinase, the hyperactivity of which was observed in cells of the MCF-7 line [ 77 ].…”

Section: Resultsmentioning

confidence: 99%

A Review of the Biological Activity of Amidrazone Derivatives

et al. 2022

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Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research.

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“…N ′, N ″‐([1,1′‐Biphenyl]‐4,4′‐diyl)bis(2‐oxopropane hydrazonoyl chloride) ( 2 ), required in this work, was synthesized by the Japp–Klingemann reaction that involved diatoziation of 1,1′‐biphenyl‐4,4′‐diamine, followed by reaction with 3‐chloropentan‐2,4‐dione in basic medium and in 50% aqueous ethanol . Reaction afforded a yellow solid product, which was collected by means of suction filtration, washed repeatedly with water, air dried, and recrystallized from dimethylformamide.…”

Section: Resultsmentioning

confidence: 99%

“…Title compound, employed as a synthon in this work, was synthesized according to a recently published procedure , which involved reacting a cold diazonium chloride, freshly obtained from 1,1′‐biphenyl‐4,4′‐diamine, with 3‐chloropentan‐2,4‐dione and sodium acetate in 50% aqueous ethanol with vigorous stirring. The yellowish‐colored product was collected by suction filtration, washed several times with cold water, dried, and recrystallized from dimethylformamide to afford the desired product in 79% yield.…”

Section: Methodsmentioning

confidence: 99%

“…In view of the interest in the activity spectrum and profile of cinnolines, and in continuation of our work on the synthesis and bioassay of new compounds of pharmacological and biological interest , the present work describes the synthesis and characterization of a number of new compounds containing bis‐piperazinylamidrazones and a series that include bicinnoline derivatives of potential anticancer and antibacterial activities with doubling of the structural motif so as to, hopefully, increase the potency. To the best of our knowledge, these compounds have not been described in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Characterization, and Bioactivity of Novel Bicinnolines Having 1‐Piperazinyl Moieties

Al-Qtaitat

El‐Abadelah

Sabri

et al. 2018

Journal of Heterocyclic Chem

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A number of novel bicinnolines containing piperazine moieties, 4a–o, were synthesized via polyphosphoric acid‐catalyzed intramolecular cyclization of the respective acyl amidrazone derivatives (3a–o). On the other hand, the amidrazones (3a–o) were prepared by reaction of N′,N″‐(biphenyl‐4,4′‐diyl)bis(2‐oxopropane hydrazonoyl chloride) (2) with the appropriate cyclic sec‐amines in the presence of trimethylamine in absolute ethanol. Structures of the newly synthesized compounds were confirmed by NMR and mass spectral data. The antitumor activity of compounds 4a–o was evaluated in vitro on human breast cancer MDA‐231 by a cell viability assay. Results revealed that compounds 4k, 4n, and 4o exhibit potential cytotoxic effects (>70%) on the cancer cells. Additionally, the antimicrobial activity of compounds 4a–o was evaluated against three clinical microbial strains: Escherichia coli (Gram‐negative bacteria), Staphylococcus aureus (Gram‐positive bacteria), and Candida albicans (fungi/yeast). Results revealed that compounds 4e and 4k exhibit good activity against all three strains included in the study and that compound 4d displays excellent activity against S. aureus strain with a minimum inhibitory concentration value of 0.187 mg/mL.

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Synthesis, characterization, and bioactivity of new bisamidrazone derivatives as possible anticancer agents

Cited by 7 publications

References 44 publications

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells

A Review of the Biological Activity of Amidrazone Derivatives

Synthesis, Characterization, and Bioactivity of Novel Bicinnolines Having 1‐Piperazinyl Moieties

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