Abstract
Fourteen diphenyl imidazoline derivatives were designed, synthesized, and identified using NMR spectroscopy and high-resolution mass spectrometry. Their cytotoxicities in HCT 116 colorectal cancer cell lines were measured using a clonogenic long-term survival assay and the half-maximal cell growth inhibitory concentration (GI50) values were in the range 3.1–58.4 μM. As the anticancer effects of diphenyl imidazolines were reported to be caused by the inhibition of mouse double minute 2 homolog (MDM2), the inhibitory effects of the most potent derivative on MDM2 were assessed through Western blotting analysis. In silico docking experiments revealed the binding mode between this derivative and MDM2.
Highlights
Fourteen diphenyl imidazoline derivatives were designed, synthesized, and identified using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry
Appl Biol Chem (2018) 61(3):303–312 diphenyl imidazolines were attributable to their inhibitory effects against mouse double minute 2 homolog (MDM2) [17,18,19,20]
MDM2 is activated by the phosphorylation of S166, which is mediated by the MEK/ERK or PI3 K/AKT pathways [39, 40]
Summary
Fourteen diphenyl imidazoline derivatives were designed, synthesized, and identified using NMR spectroscopy and high-resolution mass spectrometry Their cytotoxicities in HCT 116 colorectal cancer cell lines were measured using a clonogenic long-term survival assay and the half-maximal cell growth inhibitory concentration (GI50) values were in the range 3.1–58.4 lM. To find diphenyl imidazolines that show cytotoxicity against colorectal cancer cell lines, 14 diphenyl-imidazoline derivatives were designed and synthesized Their cytotoxicities in the HCT 116 colorectal cancer cell line were measured using a clonogenic long-term survival assay and their half-maximal cell growth inhibitory concentration (GI50) values were observed at the micromolar level. The most potent compound, (4R,5R)-2(naphthalen-2-yl)-4,5-diphenyl-imidazoline, synthesized in this study was assessed for its inhibitory effect on MDM2 by Western blotting analysis. The goal of this research was to study the structure–activity relationships (SARs) to suggest the structural features that contribute to the compound’s strong cytotoxicity
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