دورية
أعرض في EDS

Azinyl and Diazinyl Hydrazones Derived from Aryl N-Heteroaryl Ketones:  Synthesis and Antiproliferative Activity,

التفاصيل البيبلوغرافية
العنوان: Azinyl and Diazinyl Hydrazones Derived from Aryl N-Heteroaryl Ketones:  Synthesis and Antiproliferative Activity,
المؤلفون: Easmon, J., Heinisch, G., Purstinger, G., Langer, T., Osterreicher, J. K., Grunicke, H. H., Hofmann, J.
المصدر: Journal of Medicinal Chemistry; December 19, 1997, Vol. 40 Issue: 26 p4420-4425, 6p
مستخلص: A series of N-heteroaryl hydrazones derived from aryl N-heteroaryl or bis-N-heteroaryl methanones was prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Antiproliferative activity was determined in a panel of human tumor cell lines (CCRF-CEM, Burkitt's lymphoma, HeLa, ZR-75-1, HT-29, and MEXF 276L) in vitro. Generally, the new compounds were found to be more potent (IC50 = 0.011−0.436 μM) than the ribonucleotide reductase inhibitor hydroxyurea (IC50 = 140 μM). Most of the compounds exhibited the highest activity against Burkitt's lymphoma with an IC50 of 0.011−0.035 μM. [14C]Cytidine incorporation into DNA was quantitated for selected hydrazones (Z-A, E-1, Z-3, Z-4, E-5, Z-5, E-13, E-18, Z-19, Z-24, and E-26) as a measure of the inhibition of ribonucleotide reductase in Burkitt's lymphoma cells. The E-configurated compounds were found to inhibit [14C]cytidine incorporation to a greater extent (IC50 = 0.67−5.05 μM) than the Z-isomers (IC50 = 7.20 to >10 μM). Principal component analysis of the IC50 values obtained for inhibition of cell proliferation revealed that the cell lines tested can be grouped into three main families showing different sensitivities toward the compounds in our series [(i) CCRF-CEM, Burkitt's lymphoma, and Hela; (ii) HT-29; and (iii) MEXF 276 L].
قاعدة البيانات: Supplemental Index
الوصف
تدمد:00222623
15204804