Synthesis and biological evaluation of dihydromotuporamine derivatives in cells containing active polyamine transporters
Abbreviated Journal Title
J. Med. Chem.
RING-CLOSING-METATHESIS; XESTOSPONGIA-EXIGUA KIRKPATRICK; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; PROTONATION CONSTANTS; SELECTIVE DELIVERY; NUCLEIC-ACIDS; SPERMIDINE; ANALOGS; MOTUPORAMINES; Chemistry, Medicinal
Dihydromotuporamine C (4) and its 4,4-triamine analogue (5) were synthesized in good yield using ring-closing metathesis (RCM) methods. Comparison of their biological activities (K-i determinations in L1210 cells and IC50 determinations in L1210, CHO, and CHO-MG cells) revealed that the motuporamine derivatives do not use the polyamine transporter (PAT) for cellular entry. Bioevaluation of a N-1-(anthracen-9-ylmethyl)-N-1-(ethyl)homospermidine control (7) revealed that the presence of a N-1 tertiary amine center imparted a significant reduction in the PAT affinity of the polyamine conjugate and abolished its PAT-targeting selectivity.
Journal of Medicinal Chemistry
"Synthesis and biological evaluation of dihydromotuporamine derivatives in cells containing active polyamine transporters" (2005). Faculty Bibliography 2000s. 5336.