Antiviral activity of brassinosteroids derivatives against measles virus in cell cultures.
Twenty-seven brassinosteroid derivatives were tested for antiviral activity against measles virus (MV) via a virus-yield reduction assay. Compounds 6b [(22S,235)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one], 1d [(22R,23R)-2alpha,3alpha,22,23-tetrahydroxy-beta-Homo-7-oxa-stigmastan-6-one], 8a [(22R,23R)-3beta-fluoro-22,23-dihydroxystigmastan-6-one], 9b [(22S,23S)-3beta-fluoro-5alpha,22,23-trihydroxystigmastan-6-one] and 10b [(22S,23S)-5alpha-fluor-3beta,22,23-trihydroxystigmastan-6-one], with selectivity indexes (SI) of 40, 57, 31, 37 and 53, are the derivatives with good antiviral activity against MV. These SI values are higher than those obtained with ribavirin (used as reference drug). A comparative analysis of 50% cytotoxic concentration (CC50) values, using confluent non-growing cells, gives and indication of structure-activity relationship. According to their degree of cytotoxicity the compounds were divided in three groups: low, intermediate and high cytotoxicity. By observing the chemical structures of compounds belonging to the first group we can see that less cytotoxic activities are related to the presence of a 3beta-hydroxy group on C-3 (ring A) and a double bond between C-22 and C-23 (side chain). The replacement of a 5alpha-hydroxy group by a 5alpha-fluoro group enhances cytotoxicity. Halogenated brassinosteroid derivatives in C-3 position are more cytotoxic than those with an acetoxy group in the same position. For compounds 1d, 6b, 10b and ribavirin, cytotoxicity measurements were also done with replicating cells; CC50 values were low, but they still competed favourably with ribavirin against MV.
Wachsman
Mónica B
MB
Departamento de Química Biológica, Universidad de Buenos Aires, Argentina. wachsman@qb.fcen.uba.ar
Ramirez
Javier A
JA
Galagovsky
Lydia R
LR
Coto
Celia E
CE
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D005562:Formazans; D006801:Humans; D020128:Inhibitory Concentration 50; D008459:Measles virus / Q000187:drug effects* / Q000254:growth & development; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013260:Steroids, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D005562:Formazans; D013260:Steroids, Heterocyclic; D013778:Tetrazolium Salts; C079782:MTT formazan; D012254:Ribavirin