Lamellarin D Bioconjugates II: Synthesis and Cellular Internalization of Dendrimer and Nuclear Location Signal Derivatives

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1−4 were obtained in 8−84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4- to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines (MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3 and 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed, and a nuclear distribution pattern was observed for 4, which contains a nuclear localization signaling sequence.