title: A comparison of chloroambucil- and xylene-containing polyamines leads to improved ligands for accessing the polyamine transport system.
abstract: Several disubstituted arylene- and chloroambucil-polyamine conjugates were synthesized and evaluated for their ability to target cells via their polyamine transport system (PAT). As compared to the monosubstituted analogues, the disubstituted arylene systems were superior PAT targeting agents. Using a Chinese hamster ovary (CHO) cell line (PAT active) and its CHO-MG mutant (PAT inactive), the series was screened for their PAT targeting ability. The data were expressed as a CHOMG/CHO IC 50 ratio. Indeed, the disubstituted systems gave high IC 50 ratios (e.g., ratio > 2000), which indicated high selectivity for the PAT. The chloroambucil adducts were less toxic than the corresponding arylmethyl compounds. In this regard, having the proper recognition element (i.e., homospermidine) and cytotoxic "cargo" were deemed paramount for successful drug delivery via the PAT.
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, Florida 32816-2366, USA.
authors.forename: Navneet
authors.initials: N
authors.lastname: Kaur
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Delcros
authors.forename: Jon
authors.initials: J
authors.lastname: Imran
authors.forename: Annette
authors.initials: A
authors.lastname: Khaled
authors.forename: Mounir
authors.initials: M
authors.lastname: Chehtane
authors.forename: Nuska
authors.initials: N
authors.lastname: Tschammer
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Martin
authors.forename: Otto
authors.initials: O
authors.lastname: Phanstiel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D007377:Interleukin-3 / Q000378:metabolism; D008024:Ligands; D009154:Mutation; D011073:Polyamines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007377:Interleukin-3; D008024:Ligands; D011073:Polyamines; D014992:Xylenes; D002699:Chlorambucil; D013095:Spermidine