Synthesis and anticancer activities of 4-oxobenzopyrano[2,3-d]pyrimidines.
Several 2-aryl-4-oxoxbenzopyrano[2,3-d]pyrimidines have previously been shown to exhibit in vivo antitumor activity in mice with P388 lymphocytic leukemia. In the present study, a series of novel substituted benzopyrano[2,3-d]pyrimidines have been prepared and tested for cytotoxic activity against a panel of cancer cell lines including the P388 lymphocytic leukemia cell line. The unsubstituted parent compound, some methoxylated derivatives and a cyclohexyl derivative all exhibited potent cytotoxic activity (IC50 values 0.3-0.64 microM). A number of derivatives, including the unsubstituted parent pyrimidine, were shown to cause a significant perturbation in cell cycle kinetics with an observed 2- to 3-fold increase in cells in the G2/M phase of the cell cycle. Furthermore, a polymethoxylated derivative, 2-(3,4,5-trimethoxyphenyl)-9-methoxy-4-oxo-2,3-dihydrobenzopyrano[ 2,3-d]pyrimidine 13, was shown to be selectively active against a number of human ovarian cell lines.
Hadfield
J A
JA
Cancer Research Campaign Section of Drug Development and Imaging, Paterson Institute for Cancer Research, Manchester, UK. jhadfield@picr.man.ac.uk
Pavlidis
V H
VH
Perry
P J
PJ
McGown
A T
AT
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011743:Pyrimidines