title: Identification of a dibenzocyclooctadiene lignan as a HIV-1 non-nucleoside reverse transcriptase inhibitor.
abstract: BACKGROUND
  Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs.
  
  
  METHODS
  HIV-1 inhibitors were identified and biologically characterized for mechanism of action.
  
  
  RESULTS
  We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays.
  
  
  CONCLUSIONS
  This compound provides a new scaffold for further optimization of activity through structure-guided design.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Ying-Shan
authors.initials: YS
authors.lastname: Han
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Wei-Lie
authors.initials: WL
authors.lastname: Xiao
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xu
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Kramer
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Quan
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Thibault
authors.initials: T
authors.lastname: Mesplède
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Colby-Germinario
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Sun
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada mark.wainberg@mcgill.ca.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D002460:Cell Line; D034242:Cyclooctanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D018894:Reverse Transcriptase Inhibitors; C510994:dibenzocyclooctadiene lignan; D054303:HIV Reverse Transcriptase
keywords: HIV-1 inhibitors; a dibenzocyclooctadiene lignan; phenotypic cell-based assay