Clonogenic long-term survival assay of HCT 116 colorectal cancer cells after treatment with the synthesized diphenyl imidazoline derivatives
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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.
KeywordsDiphenyl imidazolines Colorectal cancer MDM2 Clonogenicity
This work was supported by the Priority Research Centers Program [NRF, 2009-0093824]. SY Shin was supported by the KU Research Professor Program of Konkuk University.
- 7.Shukla S, Bhalla M, Misra U, Mukerjee D, Saxsena AK, Sinha JN, Shanker K (1998) Cardiovascular effects of novel imidazoline congeners. Boll Chim Farm 137(7):229–232Google Scholar
- 11.Cheng YF, Hu YZ, He QJ (2005) Synthesis and antitumor activity of arylsubstituted imidazolin-2-one derivatives. Yao Xue Xue Bao 40(8):711–716Google Scholar
- 12.American Cancer Society. www.cancer.org
- 15.Berridge MV, Tan AS (1993) Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch Biochem Biophys 303(2):474–482CrossRefGoogle Scholar
- 17.Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev L, Graves B (2014) Discovery of potent and orally active p53-MDM2 inhibitors RO5353 and RO2468 for potential clinical development. ACS Med Chem Lett 5(2):124–127CrossRefGoogle Scholar
- 20.Zhang Z, Ding Q, Liu JJ, Zhang J, Jiang N, Chu XJ, Bartkovitz D, Luk KC, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B (2014) Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem 22(15):4001–4009CrossRefGoogle Scholar
- 22.Ishihara M, Togo H (2006) An efficient preparation of 2-imidazolines and imidazoles from aldehydes with molecular iodine and (diacetoxyiodo)benzene. Synlett 2:227–230Google Scholar
- 32.Gonzalez AZ, Li Z, Beck HP, Canon J, Chen A, Chow D, Duquette J, Eksterowicz J, Fox BM, Fu J, Huang X, Houze J, Jin L, Li Y, Ling Y, Lo MC, Long AM, McGee LR, McIntosh J, Oliner JD, Osgood T, Rew Y, Saiki AY, Shaffer P, Wortman S, Yakowec P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Olson SH, Sun D, Medina JC (2014) Novel inhibitors of the MDM2-p53 interaction featuring hydrogen bond acceptors as carboxylic acid isosteres. J Med Chem 57(7):2963–2988CrossRefGoogle Scholar