Design, combinatorial synthesis and biological evaluations of novel 3-amino-1′-((1-aryl-1 H -1,2,3-triazol-5-yl)methyl)-2′-oxospiro[benzo[ a ] pyrano[2,3- c ]phenazine-1,3′-indoline]-2-carbonitrile antitumor hybrid molecules

Lu, Yuanyuan; Wang, Linlin; Wang, Xiaobing; Xi, Tao; Liao, Jian-Min; Wang, Zhixiang; Jiang, Feng

doi:10.1016/j.ejmech.2017.04.040

Cited by 31 publications

(10 citation statements)

References 34 publications

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“…Additionally, the activity of 1,2,3-triazole-containing dibenzo [b, e][1,4]diazepin-11-one hybrid 83 (IC 50 : 0.71 μm, MTT assay) against A549 cells is much higher than that of 5fluorouracil (IC 50 : 3.47 μm), and this hybrid could induce the G2/M phase of cell cycle arrest and apoptosis, indicating that hybrid 83 could be used for further studies as anti-lung cancer candidates (Praveen Kumar et al, 2016). Some other compounds which are combined by 1,2,3-triazole and benzodiazepine/benzoxepine/dithiocarbamate/ deoxysalinomycin/myrrhanone B /phenanthrene/pyrano(2,3-c) phenazine/paeonol/naphthalimide/sesquiterpene/sulfonate ester/sapinofuranone/triterpene/thiourea/benzothiazinone/ benzoxazinone/furan/nimesulide (Kuntala et al, 2015;Poornima et al, 2015;Sudhapriya et al, 2015;Chandrashekhar et al, 2016;Reddy et al, 2016;Shaikh et al, 2016;Abdallah et al, 2017;Battula et al, 2017;Kumar et al, 2017;Lu et al, 2017;Mareddy et al, 2017;Mo et al, 2017;Nguyen et al, 2017;Narsimha et al, 2018;Ou et al, 2019;Yang et al, 2019;Jiang et al, 2020;Kanabar et al, 2020;Madasu et al, 2020;Qi et al, 2020;) also possess certain activity against lung cancer cell lines, but their activities are generally far inferior to those of the references. Hence, these derivatives still need further structural modifications.…”

Section: Miscellaneous 123-triazole-containing Compoundsmentioning

confidence: 99%

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Liang

Sun

et al. 2021

Front. Pharmacol.

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Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole can not only be acted as a linker to tether different pharmacophores but also serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole–containing compounds with anti–lung cancer potential, and their structure–activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti–lung cancer candidates.

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Section: Miscellaneous 123-triazole-containing Compoundsmentioning

confidence: 99%

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Liang

Sun

et al. 2021

Front. Pharmacol.

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“…We tried to screen out potential compounds that can speci cally attenuate the stemness of breast cancer cells without affecting cell viability from the phenazine-compound library we established before [25] . It was found that nine compounds (W23, W24, W49, W53, CPUL116, CPUL124, CPUL119, CPUL129, CPUL149) had little effect on breast cancer cell viability (Table1), which were chosen for the further studies.…”

Section: Resultsmentioning

confidence: 99%

Identification of A New Kind of Phenazine Compounds Attenuating The Stemness of Breast Cancer Cells Through Triggering Ferroptosis

Yang¹,

Lu²,

Zhang³

et al. 2021

Preprint

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Background: Breast cancer stem cells (BCSCs) are positively correlated with metastasis, chemoresistance and recurrence of breast cancer.Methods: The stemness were analyzed by qPCR and western blot, flow cytometry, cell spheroid formation assay, and tumor xenograft model. The cell viability was performed by MTT. The transcriptome analysis was used to evaluate the influence of these three compounds. The migration was analyzed by wound-healing assay, transwell invasion analysis, and metastasis model. The iron concentration was analyzed by fluorescence microscopy analysis. The lipid peroxidation and ROS level were analyzed by flow cytometry. The results were presented as mean ± SD, the analysis was Student’s t-test by using GraphPad Prism 5 software. P-values less than 0.05 were considered to be statistically significant. (*p < 0.05, **p < 0.01, ***p < 0.001).Results: Here, we tried to screen out small-molecule compounds targeting BCSCs from the phenazine library established by us before. We focused on the compounds without affecting cell viability and screened out three potential compounds (CPUL119, CPUL129, CPUL149) that can significantly attenuate the stemness of breast cancer cells, as evident by the decrease of stemness marker expression, CD44+/CD24- subpopulation, mammary spheroid-formation ability and tumor-initiating capacity. Additionally, these compounds suppressed the metastatic ability of breast cancer cells in vitro and in vivo. Combined with the transcriptome-sequencing analysis in breast cancer cells with or without the treatment of these three compounds, respectively, it was found that ferroptosis was shown on the top of the most upregulated pathways by CPUL119, CPUL129 and CPUL149. Mechanistically, we found that CPUL119, CPUL129 and CPUL149 could trigger ferroptosis by accumulating and sequestering iron in lysosomes through interacting with iron, and by regulating the expression of proteins (IRP2, TfR1, ferritin) engaged in modulating iron transport and storage. Furthermore, inhibition of ferroptosis rescued the suppression of these three compounds on the stemness of breast cancer cells. Conclusions: This study suggests that CPUL119, CPUL129 and CPUL149 can specifically inhibit the stemness of breast cancer cells through ferroptosis and may be the potential compounds for breast cancer treatment.

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“…Phenazine derivatives display antibacterial activity mainly against methicillin-resistant due to redox properties [17]. According to reports in recent years, phenazine derivatives possessed antiproliferative activities against various cancer cell lines [18][19][20][21]. Additionally, phenazine derivatives were candidates to be developed as inhibitors of disease-related targets and reported to show activity of inhibition to multiple enzymes [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…It supplied valuable information for further development of the TrxR1 inhibitors [24].Lu et al also designed phenazine derivatives containing phenazine, pyran, indole and 1,2,3-triazole pharmacophores. Among these derivatives, 187 (Scheme 6) demonstrated the best antiproliferative activity against A549 cancer cell line (IC 50 of 5.4 µM) and no cytotoxicity against L02 and HUVEC non-cancer cell lines[18].…”

mentioning

confidence: 99%

Advances in Phenazines over the Past Decade: Review of Their Pharmacological Activities, Mechanisms of Action, Biosynthetic Pathways and Synthetic Strategies

et al. 2021

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Phenazines are a large group of nitrogen-containing heterocycles, providing diverse chemical structures and various biological activities. Natural phenazines are mainly isolated from marine and terrestrial microorganisms. So far, more than 100 different natural compounds and over 6000 synthetic derivatives have been found and investigated. Many phenazines show great pharmacological activity in various fields, such as antimicrobial, antiparasitic, neuroprotective, insecticidal, anti-inflammatory and anticancer activity. Researchers continued to investigate these compounds and hope to develop them as medicines. Cimmino et al. published a significant review about anticancer activity of phenazines, containing articles from 2000 to 2011. Here, we mainly summarize articles from 2012 to 2021. According to sources of compounds, phenazines were categorized into natural phenazines and synthetic phenazine derivatives in this review. Their pharmacological activities, mechanisms of action, biosynthetic pathways and synthetic strategies were summarized. These may provide guidance for the investigation on phenazines in the future.

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Design, combinatorial synthesis and biological evaluations of novel 3-amino-1′-((1-aryl-1 H -1,2,3-triazol-5-yl)methyl)-2′-oxospiro[benzo[ a ] pyrano[2,3- c ]phenazine-1,3′-indoline]-2-carbonitrile antitumor hybrid molecules

Cited by 31 publications

References 34 publications

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Identification of A New Kind of Phenazine Compounds Attenuating The Stemness of Breast Cancer Cells Through Triggering Ferroptosis

Advances in Phenazines over the Past Decade: Review of Their Pharmacological Activities, Mechanisms of Action, Biosynthetic Pathways and Synthetic Strategies

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