C2-Symmetric hemiaminal ethers and diamines: new ligands for copper-catalyzed desymmetrization of meso-1,2-diols and asymmetric Henry reactions

Kałuża, Zbigniew; Bielawski, Krzysztof; Ćwiek, Rafał; Niedziejko, Piotr; Kaliski, Przemysław

doi:10.1016/j.tetasy.2013.09.011

Cited by 26 publications

(6 citation statements)

References 39 publications

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“…OM-86II was synthesized using previously standardized methods (9,11). The synthesis and physicochemical characterization of a compound 15a was presented in our previous study (11). Compound 15a (0.3 mmol; 169 mg) was dissolved in acetonitrile (15 ml) and cooled to 0°C.…”

Section: Methodsmentioning

confidence: 99%

Monoclonal anti‑MUC1 antibody with novel octahydropyrazino[2,1‑a:5,4‑a']diisoquinoline derivative as a potential multi‑targeted strategy in MCF‑7 breast cancer cells

et al. 2019

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The aim of the present study was to examine the multi-targeted potential of a monoclonal antibody against mucin-1 (MUC1) and novel octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivative (OM-86II) in estrogen receptor-positive MCF-7 human breast cancer cells. The cell viability was measured by an MTT assay. The analyses of cell cycle and disruption of mitochondrial membrane potential were performed by flow cytometry. Fluorescent microscopy and flow cytometry were used to demonstrate the effect of the compounds on apoptosis. ELISA was conducted to check the concentrations of proteins involved in multiple intracellular signaling pathways, responsible for the promotion of tumor growth and breast cancer progression, namely matrix metalloproteinase (MMP)-2, matrix MMP-9, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), soluble intercellular adhesion molecule 1 (sICAM1) and mTOR. The combination therapy based on anti-MUC1 antibody and novel OM-86II inhibited the proliferation of MCF-7 breast cancer cells. Its inhibitory effects were associated with the induction of cell cycle arrest and apoptosis. It was demonstrated that anti-MUC1 antibody with OM-86II decreased the concentrations of MMP-2, MMP-9, sICAM1 and mTOR. In addition, the combined therapy exhibited anti-inflammatory activity, which was demonstrated by a decrease in TNF-α and COX-2 concentrations. The present data provided evidence that the combination of anti-MUC1 antibody with novel OM-86II represents a multi-targeted strategy in MCF-7 breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Monoclonal anti‑MUC1 antibody with novel octahydropyrazino[2,1‑a:5,4‑a']diisoquinoline derivative as a potential multi‑targeted strategy in MCF‑7 breast cancer cells

et al. 2019

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“…The octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives ( 1, 2 ) were synthesized using previously standardized methods [ 7 – 9 ].…”

Section: Methodsmentioning

confidence: 99%

The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivatives in human gastric cancer cells

et al. 2018

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SummaryObjective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analysis and apoptosis assay were performed by standard flow cytometric method. Confocal microscopy bioimaging was used to demonstrate the expression of pivotal proteins engaged in apoptosis (caspase-8, caspase-3, p53) and cell signaling (AKT, ERK1/2). Results All compounds decreased the number of viable cells in a dose-dependent manner after 24 and 48 h of incubation, although compound 2 was a more cytotoxic agent, with IC50 values of 21 ± 2 and 6 ± 2 μM, compared to 80 ± 2 and 45 ± 2 μM for etoposide. The cytotoxic and antiproliferative effects of novel compounds were associated with the induction of apoptosis. The highest percentage of early and late apoptotic cells was observed after 48 h of incubation with compound 2 (89.9%). The value was higher compared to compound 1 (20.4%) and etoposide (24.1%). The novel diisoquinoline derivatives decreased the expression of AKT and ERK1/2. Their mechanism was associated with p53-mediated apoptosis, accumulation of cells in the G2/M phase of cell cycle and inhibition of topoisomerase II. Conclusion These data strongly support compound 2 as a promising molecule for treatment of gastric cancer.

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“…The octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives (1-7) were synthesized using previously standardized methods in the lab. [16][17][18] Stock cultures of human MCF-7 and MDA-MB-231 breast cancer cells were purchased from the American Type Culture Collection (Manassas, VA, USA). Dulbecco's minimal essential medium (DMEM) and fetal bovine serum (FBS) used in a cell culture were products of Gibco (Grand Island, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents

et al. 2017

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In this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives (1-7) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to determine apoptosis. The activity of caspases 3, 8, 9, and 10 was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The results from experiments were compared with effects obtained after incubation in the presence of camptothecin and etoposide. Our study demonstrated that the most active compounds in both analyzed breast cancer cell lines were compounds 3 and 4. We also observed that all compounds induced apoptosis. We demonstrated the higher activity of caspases 3, 8, 9, and 10, which confirmed that induction of apoptosis is associated with external and internal cell death pathway. Our study revealed that the novel compounds in group of diisoquinoline derivatives are promising candidates in anticancer treatment by activation of both extrinsic and intrinsic apoptotic pathways.

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C2-Symmetric hemiaminal ethers and diamines: new ligands for copper-catalyzed desymmetrization of meso-1,2-diols and asymmetric Henry reactions

Cited by 26 publications

References 39 publications

Monoclonal anti‑MUC1 antibody with novel octahydropyrazino[2,1‑a:5,4‑a']diisoquinoline derivative as a potential multi‑targeted strategy in MCF‑7 breast cancer cells

Monoclonal anti‑MUC1 antibody with novel octahydropyrazino[2,1‑a:5,4‑a']diisoquinoline derivative as a potential multi‑targeted strategy in MCF‑7 breast cancer cells

The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivatives in human gastric cancer cells

Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents

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