Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses
Anna A. Rubekina,
Polina N. Kamzeeva,
Vera A. Alferova,
Elena Yu. Shustova,
Ekaterina S. Kolpakova,
Elizaveta V. Yakovchuk,
Evgenia V. Karpova,
Maria O. Borodulina,
Evgeny S. Belyaev,
Alexei A. Khrulev,
Vladimir A. Korshun,
Evgeny A. Shirshin,
Liubov I. Kozlovskaya,
Andrey V. Aralov
Affiliations
Anna A. Rubekina
Faculty of Physics, M.V. Lomonosov Moscow State University, 1-2 Leninskie Gory, 119234 Moscow, Russia
Polina N. Kamzeeva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Vera A. Alferova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Elena Yu. Shustova
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Ekaterina S. Kolpakova
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Elizaveta V. Yakovchuk
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Evgenia V. Karpova
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Maria O. Borodulina
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Evgeny S. Belyaev
Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Science, 119071 Moscow, Russia
Alexei A. Khrulev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Vladimir A. Korshun
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Evgeny A. Shirshin
Faculty of Physics, M.V. Lomonosov Moscow State University, 1-2 Leninskie Gory, 119234 Moscow, Russia
Liubov I. Kozlovskaya
Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences (Institute of Poliomyelitis), 108819 Moscow, Russia
Andrey V. Aralov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.