New naphthoquinone derivatives against glioma cells

Redaelli, Marco; Mucignat‐Caretta, Carla; Isse, Abdirisak Ahmed; Gennaro, Armando; Pezzani, Raffaele; Pasquale, Riccardo; Pavan, Valeria; Crisma, Marco; Ribaudo, Giovanni; Zagotto, Giuseppe

doi:10.1016/j.ejmech.2015.04.039

Cited by 20 publications

(18 citation statements)

References 26 publications

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“…Redaelli et al. described the synthesis of juglone derivatives as potent antiproliferative agents for rat glioma (compounds VI and VII) . In addition, Tandon et al.…”

Section: Introductionmentioning

confidence: 99%

“…[16] Redaelli et al described the synthesis of juglone derivatives as potent antiproliferative agents for rat glioma (compounds VI and VII). [17] In addition, Ta ndon et al reported the anticancer activity of phenylaminophenylthio-1,4-naphthoquinones (compound VIII) and their effective induction of apoptosis in cancerc ells. [18] However,adetailed evaluation of the cytotoxicity and anticancer activities of the phenylaminophenylthio-1,4-naphthoquinone core in human cancerc ell lines has not yet been examined ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

et al. 2019

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1,4‐Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well‐known pharmaceutically active agents. Herein we report the synthesis, structural characterization, and biological evaluation of new phenylaminosulfanyl‐1,4‐naphthoquinone derivatives. We evaluated the cytotoxic activity of the synthesized compounds against three human cancer cell lines: A549, HeLa, and MCF‐7. Most of the synthesized compounds displayed potent cytotoxic activity. Specifically, compounds 5 e [3,5‐dichloro‐N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)benzamide], 5 f [N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)‐3,5‐dinitrobenzamide], and 5 p [N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)thiophene‐2‐carboxamide] showed remarkable cytotoxic activity. The synthesized compounds showed low toxicity in normal human kidney HEK293 cells. The cytotoxic mechanism of compounds 5 e, 5 f, and 5 p was explored in MCF‐7 cells. The results confirmed that these three compounds induce apoptosis and arrest the cell cycle at the G1 phase. In addition, compounds 5 e, 5 f, and 5 p were found to induce apoptosis via upregulation of caspase‐3 and caspase‐7 proteins as well as by upregulation of the gene expression levels of caspases‐3 and ‐7. Our findings demonstrate that compounds 5 e, 5 f, and 5 p could be potent agents against a number of cancer types.

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“…Redaelli et al. described the synthesis of juglone derivatives as potent antiproliferative agents for rat glioma (compounds VI and VII) . In addition, Tandon et al.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

et al. 2019

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“…An NMR‐based experiment was performed to highlight the role of the position of the substituents in the anthraquinone scaffold within the redox cycling. The reactivity in solution of compounds 2 and 4 toward Na 2 S 2 O 4 , a reducing agent, was measured by NMR . Compound 2 proved to be a better pro‐oxidant by reacting promptly with 1 equivalent of Na 2 S 2 O 4 , being partially converted to the reduced species (30%, Figures S20 and S21).…”

Section: Resultsmentioning

confidence: 99%

“…The opportune oxiranylmethyloxy anthraquinone was dissolved in 600µl of DMSO‐d6 (1mg/ml) in an NMR sample tube. After the acquisition of the reference 1 H spectrum, Na 2 S 2 O 4 (1–3 equivalents from a 10mg/ml solution in D 2 O) was added, according to a previously reported procedure . Data acquisition and processing were performed as described above.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones

Ribaudo

Ongaro

Zorzan

et al. 2019

Archiv der Pharmazie

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The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA‐binding properties were investigated using a mass spectrometry‐based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro‐oxidant redox cycling was evaluated.

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“…It was reported that some 1,4-naphthoquinone derivatives and lapachol showed strong cytotoxicity on glioma cells [10, 16]. We have previously studied the in vivo lapachol metabolism using a sensitive LC-ESI–MS n method [17], and found that lapachol was able to cross the blood brain barrier, indicating that it might be effective in treating malignant glioma.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II

Chen

Wang

et al. 2016

J Exp Clin Cancer Res

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BackgroundLapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms.MethodsThe antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexin V-FITC/PI staining, and comet assay. Effects of lapachol on topoisomerase I (TOP I) and topoisomerase II (TOP II) activities were detected by TOP I and TOP II mediated supercoiled pBR322 DNA relaxation assays and molecular docking. TOP I and TOP II expression levels in C6 cells were also determined.ResultsHigh dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats (P < 0.05). It was showed that lapachol could inhibit proliferation, induce apoptosis and DNA damage of C6 cells in dose dependent manners. Lapachol could inhibit the activities of both TOP I and II. Lapachol-TOP I showed relatively stronger interaction than that of lapachol-TOP II in molecular docking study. Also, lapachol could inhibit TOP II expression levels, but not TOP I expression levels.ConclusionThese results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro, which might be related with inhibiting TOP I and TOP II activities, as well as TOP II expression.

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New naphthoquinone derivatives against glioma cells

Cited by 20 publications

References 26 publications

Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones

Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II

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