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

Citations Over Time

Abstract

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 microM) than the ribonucleotide reductase inhibitor hydroxyurea (IC50 = 140 microM). Most of the compounds exhibited the highest activity against Burkitt's lymphoma with an IC50 of 0.011-0.035 microM. [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 microM) than the Z-isomers (IC50 = 7.20 to > 10 microM). 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].

Related Papers

• → One-Pot Synthesis of Symmetrical and Unsymmetrical Aryl Sulfides by Pd-Catalyzed Couplings of Aryl Halides and Thioacetates(2011)150 cited
• → Steric effects in the electronic spectra of substituted benzophenones III: Duryl ketones(1958)6 cited
• The Synthesis of 2-Furyltriisopropoxytitanium and its Reactivity to Carbonyl Compounds(1996)
• → ChemInform Abstract: SYNTHESIS OF ARYL THIOCYANATES FROM ARYL ALKYL SULFIDES. CONVERSION OF UNACTIVATED ARYL HALIDES INTO ARYL THIOCYANATES(1983)
• → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)