Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone

Zakharova, Olga D.; Ovchinnikova, L.P.; Goryunov, L. I.; Troshkova, Nadezhda M.; Shteingarts, V. D.; Nevinsky, Georgy A.

doi:10.1016/j.ejmech.2010.02.009

Cited by 24 publications

(8 citation statements)

References 27 publications

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“…Compound 1 inhibited the growth of LMTK (11.7 lM) and PMF (3.3 lM) cells at concentrations 2.8-9.8-fold higher than the growth of RPMI cells, while its effects on normal cells were comparable with that on MCF-7 cells (5.8 lM) (Table 1). Compound 4 inhibited the growth of LMTK cells by 50% at 30 lM, whereas the growth of PMF cells was suppressed only by 45% at significantly higher concentrations (25 lg/ml or 75.0 lM) ( Table 1) 15,16 The structures of 1-8 resemble that of F-Cpd5 and above mentioned naphtoquinones (I-VII), therefore one could expect similar effects of all these compounds on the Cdc25 phosphatases and growth of tumor cells. For RPMI cancer cells, F-Cpd5 revealed IC 50 2.1-14.8-fold higher than IC 50 of compounds 1-8, while all compounds 1-5 inhibited the growth of MCF cells 13-72-fold better than F-Cpd5 (Table 1).…”

Section: Biological Studiesmentioning

confidence: 87%

“…15,16 Interestingly, several new polyfluorinated n-alkylamino-, phenylamino-, and alkylthioderivatives of 1,4-naphthoquinone suppressed the growth of cancer cells at significantly lower concentrations than normal cells and antioxidant and mutagenic properties in the bacterial system significantly depend upon nature of the functional groups, only 3-4 of them possessing a highly promising combination of these properties. 15,16 Thus, it seems reasonable to suggest that this approach may be more rational for searching new inhibitors of Cdc25 phosphatases and tumor cell growth without side effects.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Zakharova

Ovchinnikova

Goryunov

et al. 2011

Bioorganic & Medicinal Chemistry

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Section: Biological Studiesmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 98%

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Zakharova

Ovchinnikova

Goryunov

et al. 2011

Bioorganic & Medicinal Chemistry

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“…In general terms, this work is an important contribution for developing novel antitumor drugs from lapachone group, substance currently in multiple phase II clinical trials as monotherapy and in combination with other cytotoxic drugs. 84 …”

Section: Resultsmentioning

confidence: 99%

Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair

Cavalcanti¹,

Cabral²,

Rodrigues³

et al. 2013

J. Braz. Chem. Soc.

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O presente estudo descreve a acentuada atividade citotóxica da nor-β-lapachona, seus derivados arilamino substituídos, naftoquinonas iodadas e metilada, além de nor-β-lapachonas 1,2,3-triazólicas, contra quatro linhagens de células de leucemia humana (HL-60, K562, Molt-4 e Jurkat). Nor-β-lapachonas arilamino substituídas foram identificadas com potente atividade, revelando-se como potenciais protótipos contra as linhagens tumorais descritas. Estudos utilizando o ensaio cometa evidenciaram danos ao ácido desoxirribonucleico (ADN) causado pelos derivados arilamino substituídos devido o aumento dos níveis intracelulares de espécies reativas de oxigênio (ERO's). Células de HL-60 foram selecionadas para a continuidade dos estudos de mecanismos moleculares subjacentes e apoptose induzida pelos derivados quinoidais foi observada por análise de citometria de fluxo. Cepas de Saccharomyces cerevisiae foram utilizadas para uma investigação preliminar sobre o mecanismo de ação em topoisomerases de ADN. Os estudos sugerem que, aparentemente, a citotoxidade dos compostos não envolve a inibição de topoisomerases, mas que o tratamento prejudica a atividade de reparação do ADN, provocando assim a morte celular. A capacidade em induzir apoptose e aberrações cromossômicas em fibroblastos de pulmão de hamster chinês (células V79) também foi investigada. Núcleos apoptóticos foram observados e nossos estudos indicam uma correlação entre dano ao ADN e apoptose.The current study describes that nor-β-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-β-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-β-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.Keywords: naphthoquinone, nor-β-lapachone, antileukemic activity, reactive oxygen species, genotoxicity, DNA repair Potent Antileukemic Action of...

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“…Particularly, aminoquinone structures draw interest in the literature because of the similar biological characteristics to quinone moieties (5,23,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Although they have numerous beneficial biological activities, quinone structures including pharmacophore groups could sometimes cause possible toxic effects in in vivo implementations.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of New Cyclic Aminobenzoquinones

Tuyun

Yıldız

2018

Journal of the Turkish Chemical Society Section A: Chemistry

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The aim of this research is to synthesize and characterize new members of cyclic aminobenzoquinones. Mono amino substituted products, namely 2-chloro-5,6-dimethyl-3-(pyrrolidin-1-yl)-1,4-benzoquinone (2), 2-chloro-5,6-dimethyl-3-(piperidin-1-yl)-1,4benzoquinone (3), 2-chloro-5,6-dimethyl-3-morpholino-1,4-benzoquinone (4), and 2-chloro-5,6dimethyl-3-thiomorpholino-1,4-benzoquinone (5) have been synthesized by the nucleophilic substitution reactions between 2,3-dichloro-5,6-dimethyl-1,4-benzoquinone (1) and cyclic secondary amines with a green methodology using water as solvent. Structure determination of the new products (2-5) was established on the basis of FTIR, 1 H NMR, 13 C NMR, and mass spectrometry.

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Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone

Cited by 24 publications

References 27 publications

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair

Synthesis and Characterization of New Cyclic Aminobenzoquinones

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