Azinyl and diazinyl hydrazones derived from aryl N-heteroaryl ketones: synthesis and antiproliferative activity

Journal of Medicinal Chemistry
J EasmonJ Hofmann

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 fa...Continue Reading

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jun 1, 1971·Journal of Medicinal Chemistry·B T HoL W Tansey
Aug 1, 1988·Journal of the American Chemical Society·R D CramerJ D Bunce

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Citations

Oct 23, 2001·International Journal of Cancer. Journal International Du Cancer·J EasmonJ Hofmann
Mar 15, 2005·Biochemical Pharmacology·Ruili HuangDavid G Covell
Feb 28, 2004·European Journal of Medicinal Chemistry·Luisa SaviniM Barbara Pisano
Jan 23, 2002·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Edith GössnitzerUte Wagner
Mar 25, 2017·Chemical Reviews·H Ümit KaniskanJian Jin
Feb 2, 2017·Chemical Communications : Chem Comm·Barbara CascellaLiviu M Mirica
Jan 13, 2019·Genes·Kelly E Leon, Katherine M Aird
Jul 13, 2019·Journal of Inorganic Biochemistry·Snežana K BjelogrlićNenad R Filipović
Feb 5, 2021·Journal of Medicinal Chemistry·John A GilleranDarren R Carpizo

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