New phosphorylated 5-(hydroxyalkylamino)-1,3-oxazoles as potential anticancer agents

Abstract

Eight new phosphorylated 5-(hydroxyalkylamino)-1,3-oxazoles were designed and tested for their ability to inhibit cancer cell growth. These compounds were evaluated against complete human tumor cell lines NCI-60. Only three compounds showed antitumor activity in the single dose assay, which were taken in the five dose assay. Compounds 7 and 8 showed the same average antiproliferative activity and cytotoxicity against sensitive cell lines of the general panel. However, compound 8 showed cytotoxicity to more lines than 7. By all parameters, these compounds were more active than compounds 5. Compounds 7 and 8 also showed high and similar antiproliferative activity in the concentration range GI50: 1-6 and TGI: 6-14 μM against all subpanels. Their cytotoxicity was in the concentration range of 25-54 μM. Compound 5 showed the same activity, with the exception of the leukemia, non-small cell lung cancer and ovarian cancer subpanels against which their activity was lower. When analyzing the structure-activity, it turned out that among the phosphorylated oxazole derivatives, only compounds containing the triphenylphosphonium cation (TPP+) in the 4th position of the oxazole ring exhibit antitumor activity.