{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T03:11:44Z","timestamp":1761621104400},"reference-count":0,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[1995,9,1]],"date-time":"1995-09-01T00:00:00Z","timestamp":809913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:p>Halogenated gomisin J (a derivative of lignan compound), represented by the bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12-tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was found to be a potent inhibitor of the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose, 0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24 production from acutely HIV-1-infected H9 cells. The selective indices (toxic dose\/effective dose) of these compounds were as high as &gt; 300 in some systems. 1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A 1506-resistant HIV mutant was selected and shown to possess a mutation within the RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant to 1506. Comparison of various gomisin J derivatives with gomisin J showed that iodine, bromine, and chlorine in the fourth and ninth positions increased RT inhibitory activity as well as cytoprotective activity.<\/jats:p>","DOI":"10.1128\/aac.39.9.2000","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:06:25Z","timestamp":1340841985000},"page":"2000-2007","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase"],"prefix":"10.1128","volume":"39","author":[{"given":"T","family":"Fujihashi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kaji","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Kaji","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.9.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.9.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:05:18Z","timestamp":1645473918000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.39.9.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,9]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1995,9]]}},"alternative-id":["10.1128\/AAC.39.9.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.39.9.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,9]]},"assertion":[{"value":"1995-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}