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Diffractaic acid and its ethers as anti-respiratory syncytial virus agents

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Abstract

A major secondary metabolite of lichens, diffractaic acid, was found here to exert a significant antiviral action on respiratory syncytial virus strain A2 with a EC50 of 4.8 µM while showing low toxicity to a tested cell line (CC50 of 221.9 µM). We developed methods for the synthesis of derivatives at the hydroxyl group of diffractaic acid and obtained three series of new derivatives: those of diffractaic acid and of its methyl and benzyl esters. We noted that the most promising compounds are derivatives of benzyldiffractate, which typically were found to have same or lower cytotoxicity as compared to either methyldiffractate ethers or compounds with a carboxyl group. A combination of these modifications allowed to find a promising compound: a benzyldiffractate carrying a morpholin-4-yl-ethyl substituent (EC50 2.1 µM, CC50 368.5 µM, SI 175).

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Acknowledgements

We would like to acknowledge the Chemical Research Multi-Access Center of SB RAS for the spectral and analytical measurements. The English language was corrected and certified by shevchuk-editing.com.

Author contributions

Chemistry: ASF, DUI, AAD, OAL; Analytical study: NIK; Biology: AAS, AVG, YVN, AMK, VZK; Writing - original draft preparation, review and editing: ASF, AAD, OAL, AAS; Supervision: NFS. All authors read and approved the final manuscript.

Funding

This research was funded by the Russian Science Foundation (grant No. 21-13-00026). The authors declare they have no financial interests.

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Authors and Affiliations

  1. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 9 Lavrentiev Ave., Novosibirsk, 630090, Russia

    Aleksandr S. Filimonov, Diana U. Ismangulova, Anastasia A. Diveikina, Nina I. Komarova, Olga A. Luzina & Nariman F. Salakhutdinov

  2. Smorodintsev Research Institute of Influenza, 15/17 Prof. Popov Str., Saint Petersburg, 197376, Russia

    Anna A. Shtro, Anastasia V. Galochkina, Yulia V. Nikolaeva, Artem M. Klabukov & Vera Z. Krivitskaya

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  1. Aleksandr S. Filimonov
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  2. Diana U. Ismangulova
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Correspondence to Aleksandr S. Filimonov.

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Filimonov, A.S., Ismangulova, D.U., Diveikina, A.A. et al. Diffractaic acid and its ethers as anti-respiratory syncytial virus agents. Med Chem Res 33, 677–686 (2024). https://doi.org/10.1007/s00044-024-03204-4

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