Synthesis of 26,27-bisnorcastasterone analogs and analysis of conformation-activity relationship for brassinolide-like activity

Bioorg Med Chem. 2006 Mar 15;14(6):1761-70. doi: 10.1016/j.bmc.2005.10.024. Epub 2005 Nov 8.

Abstract

Three castasterone (CS) derivatives with varied side-chain moieties, 26,27-bisnorcastasterone (20S-bisnorCS), 20-epi-26,27-bisnorcastasterone (20R-bisnorCS), and 21,26,27-trisnorcastasterone (trisnorCS), were synthesized stereoselectively from either stigmasterol or dehydroisoandrosterone. The 50% effective doses (ED50, nmol/plant) in the concentration-response curve for brassinolide-like activity in the rice lamina inclination assay were determined to be 0.020 nmol (pED50 = 10.7) for 20S-bisnorCS, 3.2 nmol (pED50 = 8.5) for 20R-bisnorCS, and 2.0 nmol (pED50 = 8.7) for trisnorCS. An analog containing an ester linkage between the steroid and the side-chain moiety of 20S-bisnorCS was also synthesized and its activity was evaluated to be 3.2 nmol (pED50 = 8.5), being equipotent to 20R-bisnorCS and trisnorCS. The activity of 20S-bisnorCS was 1/40 that of CS. The conformation analysis was conducted using a systematic search, showing that the activity decreases with an increase in the degree of freedom of the side chain of the steroidal skeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brassinosteroids
  • Cholestanols / chemical synthesis
  • Cholestanols / chemistry*
  • Cholestanols / pharmacology
  • Models, Chemical
  • Oryza / drug effects
  • Plant Growth Regulators / chemical synthesis
  • Plant Growth Regulators / chemistry*
  • Plant Growth Regulators / physiology
  • Stereoisomerism
  • Steroids, Heterocyclic / chemistry*
  • Steroids, Heterocyclic / pharmacology
  • Structure-Activity Relationship

Substances

  • Brassinosteroids
  • Cholestanols
  • Plant Growth Regulators
  • Steroids, Heterocyclic
  • castasterone
  • brassinolide