Syntheses and antiproliferative activities of novel phosphatidylcholines containing dehydroepiandrosterone moieties

Steroids. 2017 Feb:118:109-118. doi: 10.1016/j.steroids.2016.12.015. Epub 2017 Jan 4.

Abstract

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.

Keywords: Antiproliferative activity; B16; Cytotoxic; Dehydroepiandrosterone; HL-60; Phospholipids.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / adverse effects
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Biofilms / drug effects
  • Candida / drug effects
  • Candida albicans / drug effects
  • Dehydroepiandrosterone / chemistry*
  • Hemolysis / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Models, Biological
  • Molecular Structure
  • Phosphatidylcholines / adverse effects
  • Phosphatidylcholines / chemical synthesis*
  • Phosphatidylcholines / chemistry*
  • Phosphatidylcholines / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Phosphatidylcholines
  • Dehydroepiandrosterone