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GIUSEPPE DAIDONE

SYNTHESIS, CYTOTOXICITY, AND INHIBITORY EFFECTS ON TUBULIN POLYMERIZATION OF A NEW 3-HETEROCYCLO SUBSTITUTED 2-STYRYLQUINAZOLINONES

  • Autori: Raffa, D.; Edler, M.; Daidone, G.; Maggio, B.; Merikech, M.; Plescia, S.; Schillaci, D.; Bai, R.; Hamel, E.
  • Anno di pubblicazione: 2004
  • Tipologia: Articolo in rivista (Articolo in rivista)

Abstract

In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 μg ml–1 concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC50 value of 5.8 versus 3.2 μM for colchicine. It was also examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC50 values of 0.34 and 1.0 μM, respectively. At 10 μM 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 μM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly.

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