A comparison of cytotoxicity of some phosphoramides against K562 cell line

Phosphoramides with -C(O)NHP(O)- skeleton has been taken into account by the many, due to their different applications in biochemistry and agriculture. They are used as acetylcolinestrase and ureas inhibitors due to the presence of a peptide group. On the other hand, the stereochemical and pharmacological properties of six-membered phosphorus-containing heterocycles and their active role as cyclophosphamide analogs have also attracted attention. The aim of this study was to investigate the effect of position of NO2 group on phenyl ring and insertion of NH between C=O and phenyl ring, as well as their cytotoxicity against K562 cell line.

In this study, phosphoramides from carbacylamidophosphate (1-3) and N-phosphinylurea (4 – 6) groups with general formula RC(O)NHP(O)NHCH2C(CH3)2CH2NH (R = 2-NO2C6H4(1), 3-NO2C6H4(2), 4-NO2C6H4(3), 2-NO2C6H4NH(4), 3-NO2C6H4NH(5), 4-NO2C6H4(6)) were evaluated and compared to examine their cytotoxic effect against K562 cell line by applying the MTT colorimetric assay. Graph Pad PRISM version 5.0 was used to fit the data.

Biological results indicated that derivatives containing urea moiety (4-6) were higher anticancer activity than compounds (1-3) against the studied cell line. Also, derivatives with substitution 3-NO2 (2 and 5) showed higher anticancer activity than substitutions 4-NO2 (3 and 6) and 2-NO2(1 and 4).

Since hydrogen bonds play a key role in biology processes, these results suggest that increase in the hydrogen bonds of derivatives bearing urea moiety (4-6) may be increase cytotoxicity of these compounds. Moreover, the 3-NO2 group showed higher anti-cancer activity than two other positions owing to possibility electronic and steric effects.