title: Carboxyl-terminated PAMAM-SN38 conjugates: synthesis, characterization, and in vitro evaluation.
abstract: In this work, carboxyl-terminated PAMAM G-3.5 was covalently attached to SN38 via glycine and β-alanine spacers. The conjugates were stable at pH 7.4 and moderately hydrolyzed in cell culture media and rat plasma. Similarly to SN38 but to a lesser extent, both conjugates inhibited proliferation of human colorectal cancer HCT-116 cells, arrested the cell cycle in the G(2)/M phase, and led to nuclear fragmentation. However, activity of the conjugate with glycine spacer (IC(50) = 129 nM) was higher compared to that of the β-alanine linked conjugate (IC(50) = 387 nM). These PAMAM-SN38 conjugates have the potential for targeted therapy of colorectal carcinoma.
authors.affiliation: Departments of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84108, USA.
authors.forename: Nirmalkumar
authors.initials: N
authors.lastname: Vijayalakshmi
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Alexander
authors.initials: A
authors.lastname: Malugin
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004355:Drug Stability; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D000077146:Irinotecan; D002166:Camptothecin