Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype

Saueressig, Silvia; Tessmann, Josiane Weber; Mastelari, Rosiane; Silva, Liziane Pereira da; Buss, Julieti H.; Segatto, Natália Vieira; Begnini, Karine R.; Pacheco, Bruna Silveira; Pereira, Cláudio Martin Pereira de; Collares, Tiago; Seixas, Fabiana Kömmling

doi:10.1016/j.biopha.2017.12.062

Cited by 16 publications

(8 citation statements)

References 42 publications

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“…Therefore, the design, development, and implementation of potential therapeutic molecules along with unveiling the myriad of questions arising from the interaction of TNBC biological cells/drugs has been an area of intensive research in cancer drug discovery (Sebastian et al, 2016). Among organic compounds, Pyrazoles have gained attention as promising scaffolds in the field of medicinal chemistry (Saueressig et al, 2018). Possessing unique properties like anticancer, antiangiogenic, and anti-metastatic action, Pyrazole derivatives deserve credit for their varied biological activities (Lehmann et al, 2017).…”

Section: Pyrazole Derivatives Induce Apoptosis Via Ros Generation In the Triple Negative Breast Cancer Cells Mda-mb-468mentioning

confidence: 99%

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Ashourpour

Hosseini

Amini

et al. 2021

Asian Pac J Cancer Prev

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Breast cancer is one of the most common cancers among women and is a major reason for cancer death worldwide (Rakha et al., 2010). According to the literature, the incidence of female breast cancer in various countries was accounted for up to 3.2 million new cases per year by 2050 (Tao et al., 2015). Basically, breast cancer is a heterogeneous complex of diseases which involve a broad spectrum of subtypes (Yersal and Barutca, 2014).

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Section: Pyrazole Derivatives Induce Apoptosis Via Ros Generation In the Triple Negative Breast Cancer Cells Mda-mb-468mentioning

confidence: 99%

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Ashourpour

Hosseini

Amini

et al. 2021

Asian Pac J Cancer Prev

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“…Cyclization of chalcones (2a-e) into the corresponding isoxazolines (5a-e) was conducted by condensation of the chalcones with hydroxylamine hydrochloride 62 in ethanol containing a catalytic amount of piperidine to give the target derivatives. In addition, pyrazoline-1-carboxamides (6a-e) were prepared by base-catalysed cyclization of chalcones 2a-e through reaction with semicarbazide HCl 63 in absolute ethanol and piperidine (Scheme 3). The reaction mechanism for formation of carbothioamide is via the nucleophilic attack of thiosemicarbazide at b-carbon of the a-b unsaturated C¼O of chalcone followed by the proton transfer and intramolecular cyclization of molecule by the nucleophilic attack of NH 2 to carbonyl carbon which is stabilized by the proton transfer and further dehydration leads to the formation of pyrazoline (Figure 4).…”

Section: Chemistrymentioning

confidence: 99%

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors

Ali

Awad

Said

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal chemistry. Herein, we report the design, synthesis molecular modelling and biological evaluation of novel hybrids containing pyrazole, naphthalene and pyrazoline/isoxazoline moiety. Chalcones 2a-e were synthesized efficiently and were used as starting materials for synthesis of a variety of heterocycles. A novel series of pyrazoline 3a-e, phenylpyrazoline 4a-e, isoxazoline 5a-e and pyrazoline carbothioamide derivatives 6a-e were synthesized and screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide radical scavenging assay as well as 15-lipoxygenase (15-LOX) inhibition activity. Compounds 3a, 4e, 5b, 5c, 6a, 6c, and 6e showed excellent radical scavenging activity in all three methods in comparison with ascorbic acid and 15-LOX inhibition potency using quercetin as standard then were subjected to in vivo study. Catalase (CAT) activity, glutathione (GSH) and malondialdehyde (MDA) levels were assayed in liver of treated rats. Compounds 5b, 5c, and 6e showed significant in vivo antioxidant potentials compared to control group at dose of 100 mg/kg B.W. Molecular docking of compound 6a endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.

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“…The aim was to explore the interaction and combination effect between Mn III complex and two widely used drugs in cancer chemotherapy, doxorubicin, and tamoxifen, against MCF-7 and MDA-MB-231 breast cancer cells. Although doxorubicin interacts with DNA by intercalation inhibiting cancer cell growth, tamoxifen is a selective estrogen receptor modulator making them suitable for combination study due to their distinct mechanism of actions (Saueressig et al, 2018; Thorn et al, 2011; Vethakanraj & Kumar, 2017). The combination treatment results indicated the broad spectrum of synergistic effect of Mn III complex-doxorubicin combinations in inhibiting breast cancer cell growth, but the exact mechanism involved remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganese^III complex in hormone-dependent and triple negative breast cancer cells

Farghadani

Seifaddinipour

Jayakumar

et al. 2019

PeerJ

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Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. β-diiminato ManganeseIII complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou–Talalay method to investigate whether MnIII complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of MnIII complex was assessed through the acute oral toxicity test in in vivo model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC50 of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that MnIII complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, in vivo acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of MnIII complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.

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Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype

Cited by 16 publications

References 42 publications

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors

In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganese^III complex in hormone-dependent and triple negative breast cancer cells

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Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype

Cited by 16 publications

References 42 publications

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors

In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganeseIII complex in hormone-dependent and triple negative breast cancer cells

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In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganese^III complex in hormone-dependent and triple negative breast cancer cells