A comparison of chloroambucil- and xylene-containing polyamines leads to improved ligands for accessing the polyamine transport system
Abbreviated Journal Title
J. Med. Chem.
CHLORAMBUCIL-SPERMIDINE CONJUGATE; BIOLOGICAL EVALUATION; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; SELECTIVE DELIVERY; FLUORESCENT-PROBE; ESCHERICHIA-COLI; ANALOGS; DNA; CYTOTOXICITY; Chemistry, Medicinal
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.
Journal of Medicinal Chemistry
"A comparison of chloroambucil- and xylene-containing polyamines leads to improved ligands for accessing the polyamine transport system" (2008). Faculty Bibliography 2000s. 526.