Synthesis and anticancer activity of poly(ester) acemetacin conjugates

Abstract Acemetacin (ACM), a carboxymethyl ester of indomethacin, is a potent anti-inflammatory drug. However, the low solubility and is easily degraded in the stomach causes gastric mucosal dysfunction. This study. Aimed to synthetize a Janus dendrimer with polyesters, which are strong protection of the acemetacin for an efficient delivery in the targets. The dendrons with two or four acemetacin molecules were attached via azido-alkyne Click reaction to obtain the Janus dendrimers. The rates of hydrolysis at stomach conditions pH 1.4 at 37 °C showed that dendrons and Janus dendrimers are constant at different times. Janus dendrimers showed good activity against three human cells: Chronic myelogenous leukemia, mammary adenocarcinoma and lung adenocarcinoma cancer cells. The dendrons and dendrimers do not show activity against normal cells. Our study comprehensively demonstrates the advantages of polyester Janus dendrimers acemetacin delivery platform and that acemetacin conjugated with polyesters can act as anticancer agent. Graphical abstract