Discovery of colon tumor cell growth inhibitory agents through a combinatorial approach.

Article Details

Citation

Copy to clipboard

Abadi AH, Abouel-Ella DA, Lehmann J, Tinsley HN, Gary BD, Piazza GA, Abdel-Fattah MA

Discovery of colon tumor cell growth inhibitory agents through a combinatorial approach.

Eur J Med Chem. 2010 Jan;45(1):90-7. doi: 10.1016/j.ejmech.2009.09.029. Epub 2009 Sep 20.

PubMed ID

19836860 [ View in PubMed

]

Abstract

Two series with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitrile were synthesized through one pot reaction of the appropriate acetophenone, aldehyde, ammonium acetate with ethyl cyanoacetate or malononitrile, respectively. The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human HT-29 colon tumor cell line, as well as their PDE3 inhibitory activity. Compound 4-(2-Ethoxyphenyl)-2-oxo-6-thiophen-3-yl-1,2-dihydropyridine-3 carbonitrile (21) showed tumor cell growth inhibitory activity with an IC50 value of 1.25 microM. Meanwhile, 4-(4-Ethoxyphenyl)-2-imino-6-(thiophen-3-yl)-1,2-dihydropyridine-3-carbonitrile (26) showed inhibitory effect upon PDE3 using cAMP or cGMP as substrate. No correlation exists between PDE3 inhibition and the tumor cell growth inhibitory activity. Docking compound 21 to other possible molecular targets showed the potential to bind PIM1 Kinase.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE	Serine/threonine-protein kinase pim-1	IC 50 (nM)	50	N/A	N/A	Details