The novel phenylester anticancer compounds: Study of a derivative of aspirin (phoshoaspirin)

Abstract

We have synthesized a series of novel phenylester compounds and present our assessment of such a derivative of aspirin, 3-((diethoxyphosphoryloxy)methyl)phenyl 2-acetoxybenzoate, provisionally named phosphoaspirin. We determined its anticancer activity both in vitro and in vivo. Phosphoaspirin inhibited the growth of HT-29 human colon adenocarcinoma cells (IC50 = 276.6±12.3 μM (mean ± SEM)] through a combined antiproliferative and mainly proapoptotic effect. Phosphoaspirin (100 mg/kg body weight intraperitoneally daily for 21 days) also inhibited the growth of HT-29 tumors grown as xenografts in nude mice. The size of the tumors decreased progressively in the phosphoaspirin treated group, compared to controls, being reduced by 57% (p<0.001) on day 21. Phosphoaspirin achieved this effect by modulating cell kinetics; the proliferation index of cancer cells was reduced by 18.13% compared to controls (p<0.001) and the apoptosis index was increased by 94.6% (p<0.003). There was no apparent toxicity from phosphoaspirin. We conclude that phosphoaspirin is a promising agent for the control of cancer that deserves further evaluation.