title: Preparation and biological evaluation of synthetic and polymer-encapsulated congeners of the antitumor agent pactamycin: insight into functional group effects and biological activity.
abstract: The synthesis and biological analysis of a number of novel congeners of the aminocyclopentitol pactamycin is described. Specific attention was paid to the preparation of derivatives at crucial synthetic branch points of the parent structure, and biological assays revealed a number of insights into the source of pactamycin's biological activity. Additionally, the encapsulation of pactamycin and select derivatives into the PRINT© nanoparticle technology was investigated as a proof-of-concept, and evidence of bioactivity modulation through nanoparticle delivery is demonstrated. This work has provided heretofore unrealized access to a large number of novel compounds for further evaluation.
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States.
authors: Robert J
authors: RJ
authors: Sharpe
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States.
authors: Justin T
authors: JT
authors: Malinowski
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States.
authors: Federico
authors: F
authors: Sorana
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Department of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States.
authors: J Christopher
authors: JC
authors: Luft
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States.
authors: Charles J
authors: CJ
authors: Bowerman
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Department of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695-8613, United States; Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Institute for Advanced Materials, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States; Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10065-9321, United States.
authors: Joseph M
authors: JM
authors: DeSimone
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, United States. Electronic address: jsj@unc.edu.
authors: Jeffrey S
authors: JS
authors: Johnson
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D010142:Pactamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010142:Pactamycin
keywords: Nanoparticles; Pactamycin; Structural derivatization; Structure activity relationships