title: Preparation and Evaluation of a Novel Class of Amphiphilic Amines as Antitumor Agents and Nanocarriers for Bioactive Molecules.
abstract: We describe a novel class of antitumor amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.
  
  
  
  We tested the lead compound, RC16, for cytotoxicity and mechanism of cell death in several cancer cell lines, anti tumor efficacy in mouse tumor models, and ability to encapsulate chemotherapy drugs.
  
  
  
  These compounds displayed strong cytotoxic activity against cell lines derived from both pediatric and adult cancers. The IC50 of the lead compound, RC16, for normal cells including human keratinocytes, human fibroblasts and human umbilical vein endothelial cells was tenfold higher than for tumor cells. RC16 exhibited significant antitumor effects in vivo using several human xenografts and a metastatic model of murine neuroblastoma by both intravenous and oral administration routes. 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 improved the in vitro antitumor activity of these drugs as the enhancement of their aqueous solubility also improved their biologic availability.
  
  
  
  RC16 and related amphiphilic amines may be useful as a novel cancer treatment.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via S. Donato 19/2, Bologna, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Orienti
authors.affiliation: Department for Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, via Irnerio 48, Bologna, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Department for Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, via Irnerio 48, Bologna, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Teti
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Currier
authors.affiliation: College of Pharmacy and Division of Pharmaceutics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Pharmacy and Division of Pharmaceutics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.
authors.forename: Mitch
authors.initials: M
authors.lastname: Phelps
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, Ohio, USA. Timothy.Cripe@nationwidechildrens.org.|Division of Hematology/Oncology/Blood and Marrow Transplant, Nationwide Children's Hospital, 700 Children's Dr, Columbus, Ohio, 43205, USA. Timothy.Cripe@nationwidechildrens.org.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Cripe
mesh_terms: D000588:Amines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004347:Drug Interactions; D005047:Etoposide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D013501:Surface-Active Agents; D005047:Etoposide; D004317:Doxorubicin; D019158:N-Acetylneuraminic Acid; D017239:Paclitaxel
keywords: antitumor activity; encapsulation of bioactive molecules in micelles; formation of micelles in water; novel amphiphilic amines; pharmacokinetics and biodistribution