L-lysine Janus Dendrimer Conjugate with Naproxen and Mefenamic Acid and its Anticancer Activity

Dendritic architectures have potential use as excellent carriers for drug delivery due to their multifunctionality, biopermeability, and biodegradability properties. Furthermore, their conjugation with non-steroidal anti-inflammatory drugs (NSAIDs) results in a synergetic effect improving their anticancer activity. Here we report the synthesis and cytotoxic activity of novel Janus dendrimer conjugates with naproxen and mefenamic acid moieties at the periphery. Diethanolamine dendrons were convergently synthesized through a protection-deprotection sequence with naproxen as a terminal group and finally coupled to triethylene glycol as a linker. On the other hand, mefenamic acid was covalently joined to the L-lysine. The dendron and dendrimer-conjugates with naproxen and mefenamic acid showed high inhibition and selectivity against PC-3 (human prostatic adenocarcinoma), and K-562 (human chronic myelogenous leukemia) cell lines, but low cytotoxicity against normal cell lines. To explain the molecular mechanisms involved in the anticancer activity of dendrimer conjugates, our research will be continued. Dendritic architectures have potential use as excellent carriers for drug delivery due to their multifunctionality, biopermeability, and biodegradability properties. Furthermore, their conjugation with non-steroidal anti-inflammatory drugs (NSAIDs) results in a synergetic effect improving their anticancer activity. Here we report the synthesis and cytotoxic activity of novel Janus dendrimer conjugates with naproxen and mefenamic acid moieties at the periphery. The dendron and dendrimer conjugates with naproxen and mefenamic acid showed high inhibition and selectivity against PC-3 (human prostatic adenocarcinoma) and K-562 (human chronic myelogenous leukemia) cell lines but low cytotoxicity against normal cell lines.image