Synthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives

Steroids. 2007 Jan;72(1):31-40. doi: 10.1016/j.steroids.2006.10.002. Epub 2006 Nov 21.

Abstract

Starting from dehydroepiandrosterone (1) 17-picolyl (2), 17-picolinylidene (7), 17-picolinylidene-16-one (10 and 11), and 17-picolyl-16-one (15) derivatives of androst-5-ene were synthesized in one, two, four and five steps respectively. By the Oppenauer oxidation or dehydration of 2, 7, 10, and 11 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the corresponding A and B ring modified derivatives 3, 5, 6, 8, 9, and 12-14 were obtained. The structure of 2 was unambiguously proved by the appropriate X-ray structural analysis. Compounds 3, 5, 9, 12-14 showed inhibitory activity against the enzyme aromatase. Antibacterial activity, toxicity to brine shrimp Artemia salina, antitumor activity against three tumor cell lines (human cervix carcinoma HeLa cells, human melanoma FemX cells, and human myelogenous leukemia K562 cells) and toxicity against peripheral blood mononuclear cells were evaluated. Three tested compounds, namely 11, 13, and 15, showed strong activity against all three cell lines, the IC(50) values being in the range of 4-10 microM.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstenes / chemical synthesis
  • Androstenes / chemistry
  • Androstenes / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aromatase / metabolism
  • Aromatase Inhibitors / chemical synthesis
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / pharmacology*
  • Cell Line, Tumor
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Melanoma / drug therapy
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • 3-acetoxy-17-picolinylideneandrost-5-ene-16-one
  • 3-acetoxy-17-picolinylmethylandrost-5-ene-16-one
  • 3-hydroxy-17-picolinylideneandrost-5-ene-16-one
  • Androstenes
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Aromatase