Synthesis and biological activity of new 2,4,6-trisubstituted triazines as potential phosphoinositide 3-kinase inhibitors

Twenty-five novel 2,4,6-trisubstituted triazines were synthesized and biologically evaluated. Most of the compounds synthesized showed good antiproliferative activity against HCT-116 and MCF-7. Compounds B18 and B19 showed the best antiproliferative activity. Further study showed B18 and B19 inhibited four phosphoinositide 3-kinase isoforms and mammalian target of rapamycin with good potency. These results demonstrate that 2,4,6-trisubstituted triazines are potentially useful phosphoinositide 3-kinase inhibitors for the development of new anticancer drugs.

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Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002.

The EMBO Journal ◽

10.1002/j.1460-2075.1996.tb00911.x ◽

1996 ◽

Vol 15 (19) ◽

pp. 5256-5267 ◽

Cited By ~ 501

Author(s):

G. J. Brunn ◽

J. Williams ◽

C. Sabers ◽

G. Wiederrecht ◽

J. C. Lawrence ◽

...

Keyword(s):

Kinase Inhibitors ◽

Mammalian Target Of Rapamycin ◽

Target Of Rapamycin ◽

Direct Inhibition ◽

Phosphoinositide 3 Kinase

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Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:206-210 ◽

2020 ◽

Vol 19 (2) ◽

pp. 206-210

Author(s):

Feng Chen ◽

Bei Zhang

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Protein Kinase ◽

Cell Viability ◽

Cancer Cells ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Target Of Rapamycin ◽

Ovarian Cancer Cells ◽

Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

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Oxidative Stress and Apoptotic Responses Elicited by Nostoc-Synthesized Silver Nanoparticles against Different Cancer Cell Lines

Cancers ◽

10.3390/cancers12082099 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2099 ◽

Cited By ~ 3

Author(s):

Reham Samir Hamida ◽

Gadah Albasher ◽

Mashael Mohammed Bin-Meferij

Keyword(s):

Oxidative Stress ◽

Silver Nanoparticles ◽

Cancer Cells ◽

Hepg2 Cells ◽

Caspase 3 ◽

Mammalian Target Of Rapamycin ◽

B Cell Lymphoma ◽

Phosphorylated Akt ◽

Hct 116 ◽

Mcf 7

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.

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