title: [Inhibition of the replication of HIV-1 by norcantharidin in vitro].
abstract: For obtaining new structural compounds with unique resistance profiles or novel mechanisms of action on HIV-1 from natural products, anti-HIV-1 drug screening models were used in vitro. Norcantharidin (NCTD), a derivative from cantharidin, was found to have inhibitory activities on HIV-1(IIIB) p24 antigen in lymphocyte lines MT-4, CEM and H9. It inhibited HIV-1 strain 018a (sensitive to zidovudine) from replicating with EC50 (50% effective concentration) of 14.9 micromol L(-1) and also inhibited HIV-1 strain 018c (resistant to zidovudine) from replicating with EC50 of 20.2 micromol L(-1) in primary lymphocytes peripheral blood mononuclear cells (PBMC). Norcantharidin showed synergistic activity with zidovudine on HIV-1(IIIB) in MT-4 cells, the combination index was less than 0.3. But, it was not active on HIV-1 integrase, reverse transcriptase or protease in vitro. As the structure of norcantharidin is unique and different from that of all clinic drugs approved, it would be possible to obtain new and effective compounds against HIV-1 with low toxicities after modification of norcantharidin.
authors.affiliation: Institute of Medicinal and Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Zong-gen
authors.initials: ZG
authors.lastname: Peng
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: De-zhu
authors.initials: DZ
authors.lastname: Wu
authors.forename: Hong-shan
authors.initials: HS
authors.lastname: Chen
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D016655:HIV Core Protein p24 / Q000378:metabolism*; D019427:HIV Integrase / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D010447:Peptide Hydrolases / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D014779:Virus Replication; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016655:HIV Core Protein p24; D015215:Zidovudine; C069741:norcantharidin; D019427:HIV Integrase; D012194:RNA-Directed DNA Polymerase; D010447:Peptide Hydrolases; C514801:p31 integrase protein, Human immunodeficiency virus 1