Design and synthesis of 21-alkynylaryl pregnenolone derivatives and evaluation of their anticancer activity

Bioorg Med Chem. 2014 Dec 15;22(24):6980-8. doi: 10.1016/j.bmc.2014.10.012. Epub 2014 Oct 25.

Abstract

A series of novel C21-alkynylaryl derivatives of pregnenolone were synthesized and screened for anticancer activity against a panel of seven human cancer cell lines (LNCaP, A549, MCF7, HeLa, A431, HepG2, HT29). The data revealed that these compounds can be potential antitumour agents against the specific cell models. Compound 6f bearing a 2-trifluoromethylphenyl group displayed improved cytotoxicity towards all cancer cell lines used. A431 cells were the most sensitive with derivatives 6e-6h bearing electron withdrawing substituents exhibiting high potency with IC50 values ranging between 2.18 and 0.54μM and drastic inhibition of the prosurvival PI3K-Akt/PKB pathway.

Keywords: Alkynylaryl derivatives; Anticancer activity; Pregnenolone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HT29 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pregnenolone / analogs & derivatives*
  • Pregnenolone / chemical synthesis
  • Pregnenolone / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Pregnenolone
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt