Background:
Previously, we have identified 3,3′–carbonyl–bis(chromones) (1a-h, 5e)
and 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones (7a-j) as potent inhibitors of tissue
non-specific alkaline phosphatase (TNAP). The present study was designed to investigate the
cytotoxic and pro-apoptotic effect of the said derivatives.
Methods:
The anti-proliferative effect of the derivatives was investigated in three cancer cell lines
i.e., MCF-7, K-562, HeLa and normal BHK21 cells using MTT assay. The pro-apoptotic effect of
the most potent derivatives was investigated by using flow cytometry, DAPI and PI staining and
DNA binding studies.
Results:
Among all the screened compounds, 1f, 1d, 1c (from 3,3′–carbonyl–bis(chromones), 7c,
7h and 7i (from 3–(5–(benzylideneamino)thiozol–3–yl)–2H–chromen–2–ones) exhibited remarkable
growth inhibitory effects. Compounds 1f and 7c were found to be the most potent cytotoxic
derivatives against MCF-7; 1d and 7h inhibited most of the proliferation of K-562 cells, whereas
1c and 7i showed maximum growth inhibition in HeLa cells. The identified compounds exerted
lower micromolar potency against the respective cell line with significant selectivity over the normal
cells (BHK–21). The identified compounds also induced either G2 or S-phase arrest within the
respective cancer cells, chromatin condensation and nuclear fragmentation, as well as maximum
interaction with DNA.
Conclusions:
These results provide evidence that the characteristic chemical features of attached
groups are the key factors for their anticancer effects and play a useful role in revealing the
mechanisms of action in relation to the known compounds in future research programs.
Phorbol ester enhances deoxynucleoside incorporation while inhibiting proliferation of K-562 cells