Structure-activity investigations of polyamine-anthracene conjugates and their uptake via the polyamine transporter
Abbreviated Journal Title
polyamine; transport; anthracene; cytotoxicity; CHLORAMBUCIL-SPERMIDINE CONJUGATE; L1210 LEUKEMIA-CELLS; HAMSTER OVARY; CELLS; MAMMALIAN-CELLS; BIOLOGICAL EVALUATION; ALPHA-DIFLUOROMETHYLORNITHINE; CHEMOTHERAPEUTIC-AGENTS; MOLECULAR; REQUIREMENTS; SELECTIVE DELIVERY; FLUORESCENT-PROBE; Biochemistry & Molecular Biology
A series of polyamine conjugates were synthesized and evaluated for their ability to target the polyamine transporter (PAT) in two Chinese hamster ovary (CHO) cell lines (PAT-active CHO and PAT-inactive CHOMG). This systematic study identified salient features of the polyamine architecture required to target and enter cells via the PAT. Indeed, the separation of charges, the degree of N-alkylation, and the spacer unit connecting the N-1- terminus to the appended cytotoxic component (anthracene) were found to be key contributors to optimal delivery via the PAT. Using the CHO screen, the homospermidine motif (e. g., 4,4-triamine) was identified as a polyamine vector, which could enable the selective import of large N-1 -substituents (i.e., naphthylmethyl, anthracenylmethyl and pyrenylmethyl), which were cytotoxic to cells. The cell selectivity of this approach was demonstrated in B-16 murine melanoma cells and normal melanocytes (Mel- A). Three polyamine areas (recognition and transport, vesicle sequestration and polyamine-target interactions) were identified for future research.
"Structure-activity investigations of polyamine-anthracene conjugates and their uptake via the polyamine transporter" (2007). Faculty Bibliography 2000s. 7528.