Syntheses and antiproliferative activities of novel phosphatidylcholines containing dehydroepiandrosterone moieties

- Novel phosphocholines containing DHEA were synthesized.
- The antiproliferative activities of the novel phosphatidylcholines were studied.
- Incorporating DHEA at the sn-1 or sn-2 position reduces drug toxicity against normal cells (Balb/3T3).
- B16 and HL-60 cell lines were most sensitive to the tested phospholipids.

Dehydroepiandrosterone (DHEA) is a natural hormone with many beneficial properties including an anticancer activity. Unfortunately, DHEA is unstable in the body and exhibits cytotoxicity against healthy cells. In this study, a series of new phosphocholines containing DHEA at sn-1 and/or sn-2 positions were prepared. Succinic acid was used as a linker between the active drug and sn-glycero-3-phosphocholine. All the compounds were evaluated in vitro for their antiproliferative activities against four cell lines: Balb/3T3, HL-60, B16, and LNCaP. The results showed that phosphocholines with DHEA at sn-1 and/or sn-2 positions did not have cytotoxic effects on the normal cell line (Balb/3T3). Mixed-chain phospholipids with DHEA and fatty acid residues showed the highest activity against tumor cell lines. The most active compound, 11c, showed a moderate cytotoxic effect against the HL-60 and B16 cell lines.

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