Brassinosteroids: synthesis and activity of some fluoro analogues.
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.
Slavikova
Barbora
B
Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Fleming Square 2, 166 10 Prague 6, Czech Republic.
Kohout
Ladislav
L
Budesinsky
Milos
M
Swaczynova
Jana
J
Kasal
Alexander
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060406:Brassinosteroids; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002777:Cholestanols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013260:Steroids, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D060406:Brassinosteroids; D002777:Cholestanols; D017611:Fluorine Compounds; D013260:Steroids, Heterocyclic; C023623:brassinolide