Synthesis and cytotoxic effect of pregnenolone derivatives with one or two α,β-unsaturated carbonyls and an ester moiety at C-21 or C-3

Steroids. 2018 Mar:131:37-45. doi: 10.1016/j.steroids.2018.01.004. Epub 2018 Jan 31.

Abstract

Four series of pregnenolone derivatives having one or two α,β-unsaturated carbonyls and an ester moiety at C-21 or C-3 were synthetized to compare their cytotoxicity effect. The final compounds were evaluated on three human cancer cell lines: PC-3 (prostate cancer), MCF-7 (breast cancer), SKLU-1 (lung cancer) and a noncancerous cell line HGF (human gingival fibroblast). Two steroids with a 4-fluorinated benzoic acid ester at C-21 were the most active against lung cancer cell line with IC50 of 13.1 ± 1.2 and 12.8 ± 0.5 μM and showed a low percentage of cytotoxicity for noncancerous cells (27.63 ± 2.3 and 18.39 ± 1.2% in the screening at 50 μM).

Keywords: Cytotoxicity; Pregnenolone derivatives; SKLU-1; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Drug Screening Assays, Antitumor
  • Esters / chemistry*
  • Humans
  • Pregnenolone / chemical synthesis*
  • Pregnenolone / chemistry
  • Pregnenolone / pharmacology*
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Antineoplastic Agents
  • Esters
  • Pregnenolone