{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:45:59Z","timestamp":1761709559486,"version":"3.41.2"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100010099","name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences","doi-asserted-by":"crossref","award":["RVO61388963"],"award-info":[{"award-number":["RVO61388963"]}],"id":[{"id":"10.13039\/501100010099","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p> While noncanonic xanthine nucleotides XMP\/dXMP play an important role in balancing and maintaining intracellular purine nucleotide pool as well as in potential mutagenesis, surprisingly, acyclic nucleoside phosphonates bearing a xanthine nucleobase have not been studied so far for their antiviral properties. Herein, we report the synthesis of a series of xanthine-based acyclic nucleoside phosphonates and evaluation of their activity against a wide range of DNA and RNA viruses. Two acyclic nucleoside phosphonates within the series, namely 9-[2-(phosphonomethoxy)ethyl]xanthine (PMEX) and 9-[3-hydroxy-2-(phosphonomethoxy)propyl]xanthine (HPMPX), were shown to possess activity against several human herpesviruses. The most potent compound was PMEX, a xanthine analogue of adefovir (PMEA). PMEX exhibited a single digit\u2009\u00b5M activity against VZV (EC<jats:sub>50<\/jats:sub>\u2009=\u20092.6\u2009\u00b5M, TK<jats:sup>+<\/jats:sup> Oka strain) and HCMV (EC<jats:sub>50<\/jats:sub>\u2009=\u20098.5\u2009\u00b5M, Davis strain), while its hexadecyloxypropyl monoester derivative was active against HSV-1 and HSV-2 (EC<jats:sub>50<\/jats:sub> values between 1.8 and 4.0\u2009\u00b5M). In contrast to acyclovir, PMEX remained active against the TK<jats:sup>\u2013<\/jats:sup> VZV 07\u20131 strain with EC<jats:sub>50<\/jats:sub>\u2009=\u20094.58\u2009\u00b5M. PMEX was suggested to act as an inhibitor of viral DNA polymerase and represents the first reported xanthine-based acyclic nucleoside phosphonate with potent antiviral properties. <\/jats:p>","DOI":"10.1177\/2040206618813050","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T01:31:51Z","timestamp":1543541511000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Xanthine-based acyclic nucleoside phosphonates with potent antiviral activity against varicella-zoster virus and human cytomegalovirus"],"prefix":"10.1177","volume":"26","author":[{"given":"Ond\u0159ej","family":"Baszczy\u0148ski","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Maxmilian","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"\u010cesnek","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"B\u0159ehov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Jansa","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech 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