Τίτλος:
Alkyl and alkoxyethyl antineoplastic phospholipids
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Two series of phosphodiester ether lipid analogs with (N- methylmorpholino)ethyl or (N-methylpiperidino)ethyl polar head groups and long aliphatic or alkoxyethyl chains in the nonpolar portion of the molecule were synthesized as potential antineoplastic agents. The cytotoxic activity of these compounds (9-19) was evaluated in vitro against a panel of six human tumor xenografts and in two biochemical, mechanism-based screens (cdc2 kinase and cdc25 phosphatase). Analogs 13, 14, 17, and 19 showed activity in the in vitro tests. Specifically, 14 and 17 were more active than the reference compound hexadecylphosphocholine (Miltefosine, He-PC) while 13 and 19 possessed activity similar to that of the control. Of the analogs tested the one with the highest potency and least toxicity (17) has an N- methylpiperidino head group and a C16 alkyl chain. In the mechanism-based tests 11 showed weak inhibitory activity in the cdc25 phosphatase screen.
Συγγραφείς:
Koufaki, M.
Polychroniou, V.
Calogeropoulou, T.
Tsotinis, A.
Drees, M.
Fiebig, H.H.
LeClerc, S.
Hendriks, H.R.
Makriyannis, A.
Περιοδικό:
Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
antineoplastic agent; hexadecyl 2 (1 methylpiperidino)ethyl phosphate; miltefosine; phospholipid derivative; phosphonic acid derivative; unclassified drug, antineoplastic activity; article; cancer graft; cytotoxicity; drug effect; drug potency; drug screening; human; human cell; human tissue, Animals; Antineoplastic Agents; CDC2 Protein Kinase; cdc25 Phosphatase; Cell Cycle Proteins; Cyclins; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Mitosis; Molecular Structure; Neoplasm Transplantation; Neoplasms, Experimental; Organophosphorus Compounds; Phospholipids; Phosphonic Acids; Phosphoprotein Phosphatase; Piperidines; Starfish; Tumor Cells, Cultured
