Abstract
A natural brassinosteroid and a series of synthetic derivatives were found to be good inhibitors of herpes simplex virus type 1 (HSV-1) and arenavirus replication in cell culture. The synthetic compounds tested were analogues of the 24(S) ethylbrassinone. Compounds (22R,23R,24S)-2α, 3α,5α,22,23-pentahydroxy-stigmastan-6-one and (22R,23R,24S)-3β-bromo-5α,22,23-trihydroxy stigmastan-6-one were cytotoxic at concentrations of 20–40 µM. (22S,23S,24S)-2α,3α,22,23-tetrahydroxy-5α,stigmastan-6-one, (22R,23R,24S)-3β-acetoxy-22,23-dihydroxy-5α-cholestan-6-one, (22S,23S,24S)-3β-bromo-22,23-dihydroxy-5α-cholestan-6-one and (22S,23S,24S)-3β-bromo-5α,22,23-trihydroxy-stigmastan-6-one were the most active of the series against HSV-1, with selectivity index (SI) values (CC50/EC50) ranging from 10.6 to 16.5. The majority of the compounds were potent inhibitors of arenaviruses, (22S,23S,24S)-3β-bromo-5α,22,23-trihydroxy-stigmastan-6-one being the most active, with SI values of 307.8 and 692.5 for Tacaribe and Junin viruses, respectively. The antiviral activity of brassinosteroid derivatives was not because of direct inactivation; time-of-addition experiments suggested that a late step in HSV-1 multiplication was affected, whereas arenaviruses remained susceptible to the compounds throughout the replicative cycle.