Preparation and cytotoxic evaluation of new steroidal oximes and aza-homosteroids from diosgenin and cholesterol

Steroids. 2022 Jun:182:109012. doi: 10.1016/j.steroids.2022.109012. Epub 2022 Mar 16.

Abstract

Using cholesterol and diosgenin as starting materials, we have designed a straightforward methodology to prepare in a reduced number of steps a novel series of steroidal oximes and their aza-homolactam analogs with four types of side chains: cholestane, spirostane, 22-oxocholestane and 22,26-epoxycholestene. The products were evaluated for their cytotoxic activity against the MCF-7 breast cancer cell line. Moreover, the selectivity of the most active compounds was determined against peripheral blood lymphocytes. Compounds 5, 8 and 13 were found to be the most active derivatives, exhibiting IC50 values in the low micromolar range (7.9-9.5 µM) and excellent selectivities (IC50 > 100 µM) against the non-tumor cell line.

Keywords: 3,6-Dihydroxyimino derivatives; A-homolactams; B-homolactams; MCF-7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholesterol / pharmacology
  • Diosgenin* / pharmacology
  • Drug Screening Assays, Antitumor
  • Homosteroids / pharmacology
  • Molecular Structure
  • Oximes / pharmacology
  • Steroids / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Homosteroids
  • Oximes
  • Steroids
  • Cholesterol
  • Diosgenin