posted on 2005-10-06, 00:00authored byJanez Mravljak, Reiner Zeisig, Slavko Pečar
Alkylphospholipid analogues of perifosine and miltefosine bearing a nitroxide moiety at different
positions on an alkyl chain were synthesized as electron paramagnetic resonance (EPR) probes.
Their amphiphilic properties were characterized by determining their critical micelle concentration (cmc) and hemolytic activity on erythrocytes both in free and liposomal form. Spin-labeled
analogues as membrane components of large unilamellar liposomes containing cholesterol and
dicetyl phosphate or in free solution were evaluated using the MTT assay to determine growth
inhibition on MT1, MT3, and MCF7 breast cancer cell lines. 4a (IC50 = 56.4 μM) was found to
be significantly more active than the perifosine against the MCF-7 cell line. Its high cmc
(194.03 μM) and low hemolytic activity shows that its cytotoxic activity might be more specific;
therefore, 4a can be an important molecular tool for further EPR investigations.