Quinazolines are multitarget agents, which have broad spectrum of
biological activity, and some of them are now in
cancer clinical testing. 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]
quinazoline is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects on
cancer cell lines HeLa and B16.
Quinazoline, at micromolar concentrations, induced morphological changes and
necrosis of B16 cells, and at nanomolar concentrations it produced changes of
F-actin cytoskeleton. It did not cause changes in the cell cycle, did not induce apoptotic cell death in B16 cells, did not have a mutagenic effect, and did not even behave as a typical
intercalating agent. Little significant reduction of
tumor volume in intramuscular transplanted B16 cells was observed. The aim of the present study was to examine the cytotoxic effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]
quinazoline on murine
leukemia L1210 cells and fibroblast NIH-3T3 cells. Induction of cell morphology and cell cycle changes, induction of apoptosis and
caspase 3 activity were studied.
Quinazoline acted cytotoxically on both cell lines. The sensitivity of
leukemia L1210 cells to the
quinazoline was higher than that of fibroblast NIH-3T3. The IC(100) was 12 microM for L1210 cells and 24 microM for NIH-3T3 cells. No effect of
quinazoline on the cell cycle profile of L1210 and NIH-3T3 was detected, however,
quinazoline induced an increase of the sub-G(0) cell fraction, apoptotic DNA fragmentation, and apoptotic morphological changes at a concentration of 12 microM. This
quinazoline concentration induced
caspase 3 activity. Our results demonstrated that induction of apoptotic cell death via activation of
caspase 3 contributed to the cytotoxic effects of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]
quinazoline in murine
leukemia L1210 cells.