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RCn

A Novel Class of Amphiphilic Amines as Antitumor Agents and Nanocarriers for Bioactive Molecules

rcn

Dr Isabella Orientiand Dr.Timothy P. Cripe et al. developed a novel class of antitumor amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length. Anticancer activity of the RCn amines was observed in all of the cancer cell lines analysed, including both pediatric and adult tumors. The lead compound, RC16, displayed strong cytotoxic activity and was chosen for further study. The IC50 of RC16 for normal cells was tenfold higher than for tumor cells. RC16 exhibited significant antitumor effects in vivo in several cancer models by both intravenous and oral administration routes. RC16 strongly improved the survival in the metastatic model. The amphiphilic amines bind to and induce anticancer activityby several mechanisms of action with differential effects on normal cells, resulting in a clinically significant therapeutic window.

In addition to its activity as an antitumor drug, amphiphilic amines (RCn) are useful for encapsulating traditional chemotherapies and thereby enhancing their efficacy and reducing their side effects. RC16 has been evaluated for its ability to complex other bioactive molecules. The amphiphilic character of RC16 triggered a spontaneous molecular self-assembling in water with formation of micelles allowing complexation of Doxorubicin, Etoposide and Paclitaxel. These micelles significantly improvedthe in vitro antitumor activity of these drugs as the enhancement of their aqueous solubility also improved their biologic availability. Thus, RC16 and related amphiphilic amines may be useful as a novel cancer treatment.

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