{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:23:27Z","timestamp":1790735007363,"version":"4.1.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI104494"],"award-info":[{"award-number":["R01 AI104494"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["SC1 GM111158"],"award-info":[{"award-number":["SC1 GM111158"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005332","name":"Alpha Omega Alpha Honor Medical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as \u03b2-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic \u03b1-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the \u03b1-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 \u03bcM, and 10 compounds inhibited HSV-1 and HSV-2 at 5 \u03bcM, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC\n            <jats:sub>50<\/jats:sub>\n            ) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC\n            <jats:sub>50<\/jats:sub>\n            ] of 50 to &gt;100 \u03bcM). Therapeutic indexes ranged from &gt;170 to &gt;1,200. These data indicate that troponoids and specifically \u03b1-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants.\n          <\/jats:p>","DOI":"10.1128\/aac.02675-15","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T03:58:43Z","timestamp":1453262323000},"page":"2140-2149","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Synthetic \u03b1-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses"],"prefix":"10.1128","volume":"60","author":[{"given":"Peter J.","family":"Ireland","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Tavis","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"D'Erasmo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA"},{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle R.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA"},{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Murelli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA"},{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Cadiz","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindi S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Korom","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen A.","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda A.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1823","volume-title":"Fields virology","author":"Roizman B","year":"2013","unstructured":"Roizman B, Knipe DM, Whitley RJ. 2013. Herpes simplex viruses, p 1823\u20131897. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed), Fields virology, 6th ed. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/591913"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200101000-00001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103151"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis891"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/07448481.2010.483711"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01336-09"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3200\/JACH.57.4.389-394"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.olq.0000204723.15765.91"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit458"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.07.046128"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/338231"},{"key":"e_1_3_3_14_2","first-page":"447","article-title":"Genital herpes and human immunodeficiency virus: double trouble","volume":"82","author":"Celum C","year":"2004","unstructured":"Celum C, Levine R, Weaver M, Wald A. 2004. Genital herpes and human immunodeficiency virus: double trouble. Bull World Health Organ 82:447\u2013453.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1332802"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61750-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-405880-4.00001-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.1.114-128.2003"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldt011"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2010.01356.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.08.013"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.1.76"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.04.002"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2011.06.009"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.03.014"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/590668"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit350"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(02)00093-1"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/OLQ.0b013e3181bcaf91"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(92)90335-9"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit592"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.256"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00142-3"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03875-14"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.06.007"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4md00055b"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.41.862"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.03.025"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki268"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2000757"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.4884-4894.2005"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2009.09.016"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04617-14"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2010.124"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.22.5.824"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo9915731"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9634278"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.020321"},{"key":"e_1_3_3_49_2","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1055\/s-1986-31713","article-title":"An improved synthesis of 2,7-dihydroxytropolone (2-hydroxytrolone)","volume":"7","author":"Takeshita H","year":"1986","unstructured":"Takeshita H, Mori A, Kusaba T. 1986. An improved synthesis of 2,7-dihydroxytropolone (2-hydroxytrolone). Synthesis 7:578\u2013579.","journal-title":"Synthesis"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.09.037"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol302892g"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo401617r"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02559-12"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.51.3.747-753.1984"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.3.1077-1088.2002"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.8.3882-3894.1990"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.43.1.314-324.1982"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0328"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1947"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5716"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1086\/606028"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(02)00263-9"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00056-14"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2015.08.014"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1086\/432766"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00088-1"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.08.008"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071006"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(98)00078-7"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90066-3"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00374-12"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.66.1.347"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002862"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.03.015"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.5.1707-1713.2003"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.66.404"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00311-13"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02675-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02675-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:36:33Z","timestamp":1645475793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02675-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":76,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1128\/AAC.02675-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02675-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]},"assertion":[{"value":"2015-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}