Lewis acid-induced intramolecular access to novel steroidal ring D-condensed arylpyrazolines exerting in vitro cell-growth-inhibitory effects

Mol Divers. 2015 Aug;19(3):511-27. doi: 10.1007/s11030-015-9593-3. Epub 2015 Apr 18.

Abstract

Novel androstenoarylpyrazolines were synthesized stereoselectively by the BF3-induced intramolecular 1,3-dipolar cycloaddition of alkenyl hydrazones obtained from a steroidal D-seco-aldehyde with differently substituted arylhydrazines. The reaction rates were observed to be affected significantly by the electronic character of the substituents on the aromatic moiety. The cyclizations are assumed to follow a stepwise rather than a pure concerted mechanism, to afford arylpyrazolidines as primary products. Spontaneous oxidation of the saturated N,N-heterocycles under the reaction conditions led to pyrazoline derivatives in good to excellent yields. In in vitro antiproliferative studies on a panel of breast cancer cells (MCF7, T47D, MDA-MB-231, and MDA-MB-361), some of the 3-deacetylated cycloadducts exerted marked growth inhibitory activities, with IC(50) values in the range 3.56-9.32 μm, which are comparable to that for the reference agent cisplatin.

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
  • Drug Screening Assays, Antitumor
  • Humans
  • Lewis Acids / chemistry*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Steroids / chemistry*

Substances

  • Antineoplastic Agents
  • Lewis Acids
  • Pyrazoles
  • Steroids