Cationic Amphiphilic Dendrons with Anticancer Activity

Cancer has become the leading cause of human deathworldwide, and there is an urgent need to design and develop new oncologydrugs. In this study, we report series of cationic amphiphilic dendrons withdifferent hydrophobic alkyl chains (Cn) and different generations (Gx) anddemonstrate their use for anticancer applications. The results revealed thatlower-generation dendrons (G1) with a longer hydrophobic alkyl chain (C12and C18) have stronger antitumor activity. Among these dendrons, a leadcandidate C12-G1was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatictumor cells, while simultaneously, hemolysis was negligible. Mechanisticstudies showed that C12-G1could lead to cytoplasmic leakage and inducecancer cell necrosis through membrane disruption. In addition, C12-G1showed potent inhibition of tumor growth in a B16-F10 melanoma model. In conclusion, thesefindings demonstrate that thecationic amphiphilic dendron might be a promising agent for anticancer application