Wachsman M B, López E M, Ramirez J A, Galagovsky L R, Coto C E
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Antivir Chem Chemother. 2000 Jan;11(1):71-7. doi: 10.1177/095632020001100107.
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 (22 R,23 R,24S)-2alpha, 3alpha,5alpha,22,23-pentahydroxy-stigmastan-6-one and (22R,23R,24S)-3beta-bromo-5alpha,22,23-trihydroxy stigmastan-6-one were cytotoxic at concentrations of 20-40 microM. (22S,23S,24S)-2alpha,3alpha,22,23-tetrahydroxy-5alpha, stigmastan-6-one, (22R,23R,24S)-3beta-acetoxy-22,23-dihydroxy-5alpha-choles tan-6-one, (22S,23S,24S)-3beta-bromo-22,23-dihydroxy-5alpha-cholestan-6 -one and (22S,23S,24S)-3beta-bromo-5alpha,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)-3beta-bromo-5alpha,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.
一种天然油菜素甾体和一系列合成衍生物被发现是单纯疱疹病毒1型（HSV-1）和沙粒病毒在细胞培养中复制的良好抑制剂。所测试的合成化合物是24(S) - 乙基油菜素甾酮的类似物。化合物(22R,23R,24S)-2α, 3α,5α,22,23 - 五羟基 - 豆甾 - 6 - 酮和(22R,23R,24S)-3β - 溴 - 5α,22,23 - 三羟基豆甾 - 6 - 酮在浓度为20 - 40微摩尔时具有细胞毒性。(22S,23S,24S)-2α,3α,22,23 - 四羟基 - 5α - 豆甾 - 6 - 酮、(22R,23R,24S)-3β - 乙酰氧基 - 22,23 - 二羟基 - 5α - 胆甾 - 6 - 酮、(22S,23S,24S)-3β - 溴 - 22,23 - 二羟基 - 5α - 胆甾 - 6 - 酮和(22S,23S,24S)-3β - 溴 - 5α,22,23 - 三羟基 - 豆甾 - 6 - 酮是该系列中对HSV-1最具活性的，选择性指数（SI）值（CC50/EC50）范围为10.6至16.5。大多数化合物是沙粒病毒的有效抑制剂，(22S,23S,24S)-3β - 溴 - 5α,22,23 - 三羟基 - 豆甾 - 6 - 酮活性最高，对塔卡里伯病毒和胡宁病毒的SI值分别为307.8和692.5。油菜素甾体衍生物的抗病毒活性并非由于直接灭活；添加时间实验表明，HSV-1增殖的后期步骤受到影响，而沙粒病毒在整个复制周期中对这些化合物仍敏感。
