{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:17:08Z","timestamp":1787163428345,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018M3A9H4089601"],"award-info":[{"award-number":["NRF-2018M3A9H4089601"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018M3A9H4089602"],"award-info":[{"award-number":["2018M3A9H4089602"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["SI2132-20"],"award-info":[{"award-number":["SI2132-20"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Influenza viruses are one of the major causative agents for human respiratory infections. Currently, vaccines and antivirals approved for preventing and treating viral infections are available. However, limited protection efficacy and frequent emergence of drug-resistant viruses stand for a need for the development of antivirals with different chemical skeletons from existing drugs. Screening of a chemical library identified an isoquinolone compound (1) as a hit with 50% effective concentrations (EC50s) between 0.2 and 0.6 \u00b5M against the influenza A and B viruses. However, it exhibited severe cytotoxic effects with a 50% cytotoxic concentration (CC50) of 39.0 \u00b5M in canine kidney epithelial cells. To address this cytotoxic issue, we synthesized an additional 22 chemical derivatives. Through structure-activity, as well as structure-cytotoxicity relationship studies, we discovered compound 21 that has higher EC50 values ranging from 9.9 to 18.5 \u00b5M, but greatly alleviated cytotoxicity with a CC50 value over 300 \u00b5M. Mode-of-action and cell type-dependent antiviral experiments indicated that it targets viral polymerase activity and functions also in human cells. Here, we present a new class of viral polymerase inhibitors with a core skeleton of isoquinolone, of which antiviral activity could be better improved through following design and synthesis of its derivatives for drug development.<\/jats:p>","DOI":"10.3390\/ph14070650","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T11:36:44Z","timestamp":1625571404000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Antiviral Activity of Isoquinolone Derivatives against Influenza Viruses and Their Cytotoxicity"],"prefix":"10.3390","volume":"14","author":[{"given":"Yejin","family":"Jang","sequence":"first","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhe","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjin","family":"Shin","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jea","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2851-5298","authenticated-orcid":false,"given":"Meehyein","family":"Kim","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"},{"name":"Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D49","DOI":"10.1016\/j.vaccine.2008.07.039","article-title":"The biology of influenza viruses","volume":"26","author":"Bouvier","year":"2008","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41586-019-1530-7","article-title":"Structures of influenza A virus RNA polymerase offer insight into viral genome replication","volume":"573","author":"Fan","year":"2019","journal-title":"Nature"},{"key":"ref_3","unstructured":"(2021, April 29). 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