Ether lipid derivatives: antineoplastic activity in vitro and the structure-activity relationship.

Abstract

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH3 and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppressed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 micrograms/ml). ET-18-OCH3 did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH3 seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 micrograms/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1-10 micrograms/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity. In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [3H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: W E Berdel, D D Von Hoff, C Unger, H D Schick, U Fink, A Reichert, H Eibl, J Rastetter
• Journal: Lipids (Lipids) Vol. 21 Issue 4 Pg. 301-4 (Apr 1986) ISSN: 0024-4201 [Print] United States
• PMID: 3713449 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Lysophosphatidylcholines
• Phospholipid Ethers
• Piperidines
• edelfosine
• CP 46665

Topics

• Antineoplastic Agents (therapeutic use)
• Cell Survival (drug effects)
• Female
• Humans
• Lysophosphatidylcholines (therapeutic use, toxicity)
• Neoplasms (drug therapy, pathology)
• Phospholipid Ethers
• Piperidines (therapeutic use, toxicity)
• Structure-Activity Relationship