Ugi reaction in the synthesis of Janus dendrimers as nanocarriers of chlorambucil and ibuprofen

The synthesis and characterization of Janus dendrimers conjugated with two drugs: chlorambucil and ibuprofen are reported. The dendrons by the Ugi reaction were obtained. The 2-aminoethanol, 3-aminopropanol and 5-aminopentanol were used as the amine resources, which allowed obtaining several Ugi adducts with different aliphatic chain lengths. The newly Janus dendrimers compounds were evaluated against human cancer cell lines. The Janus dendrimer from 2-aminoethanol in the length of the aliphatic chain showed potent activity againts prostatic adenocarcinoma PC-3 (IC 50 8.88 ± 0.7) and mammary adenocarcinoma MCF-7 (IC 50 9.14 ± 1.0) μM. In addition, the feasibility of incorporating different drugs in the reaction was verified, which opens new possibilities for the functionalization of dendrimers in the therapeutic context. • Synthesis of new Janus dendrimers via Ugi-4C reactions functionalized with ibuprofen and chlorambucil. • The dendrons were obtained with amino alcohols, ethyl isocyanoacetate, formaldehyde and carboxylic acid from ibuprofen or chlorambucil. • The dendrimers were obtained by Steglisch reaction with DCC and DPTS in CH 2 Cl 2 . • The anticancer studies the Janus dendrimer with 2-amino-1-ethanol showed significant activity. • No cytotoxic effects of dendrons and dendrimers on the kidney COS-7 cell line was observed.