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Novel ether lipids as antineoplastic agents

Novel ether lipids as antineoplastic agents
Novel ether lipids as antineoplastic agents

A range of ether lipids that show in vitro antineoplastic activity were synthesised. These compounds include: alkyl lysophospholipid, lysophospholipid and alkyl phospholipid analogues, which all share the feature of having heterocyclic phosphorus-containing headgroup moieties. These headgroups were synthesised using phosphorus (V) chemistry.

The versatility of phosphorus (V) chemistry in synthesising heterocyclic moieties has been demonstrated for five, six and also seven membered rings. Lysophospholid analogues with six-membered heterocyclic headgroups were synthesised directly from the 3-O-alkyl-rac-glycerol without prior protection of the position-2 hydroxyl. Six membered phosphorus-containing heterocycles were found to be particularly stable, and the cyclic phosphochloridates, 5-alkyl-2-chloro-1,3-dioxa-2-phosphacyclohexane-2-oxides were prepared from the corresponding 2-alkyl-1,3-propanediols. Additionally using the cyclic phosphochlorides we were able synthesise two homologous series of either lipid analogues, namely the 5-alkyl-2-hydroxy-1,3-dioxa-2-phosphacyclohexane-2-oxides and their sodium salts, the 5-alkyl-2-hydroxy-1,3-dioxa-2-phosphacyclohexane-2-oxides sodium salts. These compounds were synthesised in order to study the effect of the degree of ionisation on biological activity.

All ether lipid analogues synthesised were assayed for their biological activity. The cytotoxicity data obtained from in vitro assays have provided insights into relationships between chemical structure and biological activity. In particular, these data have indicated that the ability of amphiphiles to induce cytostatis in cancer cell lines is correlated to the overall size of the hydrophilic headgroup. Furthermore, it has been observed that for several of the compounds synthesised the concentrations at which 50% cell death occurs lies almost one order of magnitude below the critical micelle concentration, indicating a non-detergent based mechanism.

University of Southampton
Wan, Jung Wing
aa93a34b-5c7f-4791-9686-ebdc4cbfbbea
Wan, Jung Wing
aa93a34b-5c7f-4791-9686-ebdc4cbfbbea

Wan, Jung Wing (1997) Novel ether lipids as antineoplastic agents. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

A range of ether lipids that show in vitro antineoplastic activity were synthesised. These compounds include: alkyl lysophospholipid, lysophospholipid and alkyl phospholipid analogues, which all share the feature of having heterocyclic phosphorus-containing headgroup moieties. These headgroups were synthesised using phosphorus (V) chemistry.

The versatility of phosphorus (V) chemistry in synthesising heterocyclic moieties has been demonstrated for five, six and also seven membered rings. Lysophospholid analogues with six-membered heterocyclic headgroups were synthesised directly from the 3-O-alkyl-rac-glycerol without prior protection of the position-2 hydroxyl. Six membered phosphorus-containing heterocycles were found to be particularly stable, and the cyclic phosphochloridates, 5-alkyl-2-chloro-1,3-dioxa-2-phosphacyclohexane-2-oxides were prepared from the corresponding 2-alkyl-1,3-propanediols. Additionally using the cyclic phosphochlorides we were able synthesise two homologous series of either lipid analogues, namely the 5-alkyl-2-hydroxy-1,3-dioxa-2-phosphacyclohexane-2-oxides and their sodium salts, the 5-alkyl-2-hydroxy-1,3-dioxa-2-phosphacyclohexane-2-oxides sodium salts. These compounds were synthesised in order to study the effect of the degree of ionisation on biological activity.

All ether lipid analogues synthesised were assayed for their biological activity. The cytotoxicity data obtained from in vitro assays have provided insights into relationships between chemical structure and biological activity. In particular, these data have indicated that the ability of amphiphiles to induce cytostatis in cancer cell lines is correlated to the overall size of the hydrophilic headgroup. Furthermore, it has been observed that for several of the compounds synthesised the concentrations at which 50% cell death occurs lies almost one order of magnitude below the critical micelle concentration, indicating a non-detergent based mechanism.

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Published date: 1997

Identifiers

Local EPrints ID: 463103
URI: http://eprints.soton.ac.uk/id/eprint/463103
PURE UUID: ff34d80e-0611-4a48-a03a-f7bf1a83c367

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Date deposited: 04 Jul 2022 20:44
Last modified: 23 Jul 2022 01:09

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Author: Jung Wing Wan

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