New chemical agents based on adamantane-monoterpene conjugates against orthopoxvirus infections

• Published in: MedChemComm 2020-10, Vol.11 (1), p.1185-1195
• Main Authors: Suslov, Evgenii V, Mozhaytsev, Evgenii S, Korchagina, Dina V, Bormotov, Nikolay I, Yarovaya, Olga I, Volcho, Konstantin P, Serova, Olga A, Agafonov, Alexander P, Maksyutov, Rinat A, Shishkina, Larisa N, Salakhutdinov, Nariman F
• Format: Article
• Language: English
• Subjects: Acids; Amides; Chemical agents; Cidofovir; Cowpox; Cytotoxicity; Epidemics; Low molecular weights; Molecular weight; Pinene; Selectivity; Smallpox; Toxicity; Viruses
• ISSN: 2632-8682; 2040-2503; 2632-8682; 2040-2511
• DOI: 10.1039/d0md00108b

Currently, the spectrum of agents against orthopoxviruses, in particular smallpox, is very narrow. Despite the fact that smallpox is well controlled, there is, for many reasons, a real threat of epidemics associated with this or a similar virus. In order to search for new low molecular weight orthopoxvirus inhibitors, a series of amides combining adamantane and monoterpene moieties were synthesized using 1- and 2-adamantanecarboxylic acids as well as myrtenic, citronellic and camphorsulfonic acids as acid components. The produced compounds exhibited high activity against the vaccinia virus (an enveloped virus belonging to the poxvirus family), which was combined with low cytotoxicity. Some compounds had a selectivity index higher than that of the reference drug cidofovir; the highest SI = 1123 was exhibited by 1-adamantanecarboxylic acid amide containing the (−)-10-amino-2-pinene moiety. The produced compounds demonstrated inhibitory activity against other orthopoxviruses: cowpox virus (SI = 30-406) and ectromelia virus (mousepox virus, SI = 39-707). The first example of adamantane derivatives containing monoterpene moieties that showed inhibitory activity against several orthopoxviruses.