Brassinosteroids: synthesis and activity of some fluoro analogues.

Abstract

Three types of 5alpha-androstane and ergostane analogues of brassinolide, containing a fluorine atom in either the 3alpha or the 5alpha positions or in 3alpha and 5alpha positions, were prepared using standard operations (reaction of 3beta-alcohols with (diethylamino)sulfur trifluoride, cleavage of epoxide with HF in py or BF 3.Et 2O). The 5alpha-fluorine was found to affect chemical reactivity (e.g., electrophilic addition to the Delta (2)-double bond) as well as physical properties (e.g., NMR, chromatographic behavior) of the products. Cytotoxicity of the products was studied using human normal and cancer cell lines with 28-homocastasterone as positive control and their brassinolide type activity was established using the bean second-internode test with 24-epibrassinolide as standard. The equivalence of F and OH groups was observed in some of the active compounds. The anticancer and the brassinolide-type activity do not correlate with each other: ergostane derivatives were most active in the former test while androstane derivatives were best in the latter.

• Authors: Barbora Slavikova, Ladislav Kohout, Milos Budesinsky, Jana Swaczynova, Alexander Kasal
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 13 Pg. 3979-84 (Jul 10 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18557605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Brassinosteroids
• Cholestanols
• Fluorine Compounds
• Steroids, Heterocyclic
• brassinolide

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Brassinosteroids
• Cell Line
• Cell Survival (drug effects)
• Cholestanols (chemical synthesis, chemistry, pharmacology)
• Fluorine Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Molecular Structure
• Steroids, Heterocyclic (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship