Suksdorfin: an anti-HIV principle from Lomatium suksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti-AIDS nucleosides.
Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937. Combinations of 1 and the anti-HIV nucleosides ddI and ddC demonstrated statistical synergy in inhibiting HIV-1 replication (ddC > ddI). However, the viral inhibition mediated by combining 1 with AZT was not statistically synergistic. Furthermore, the presence of suksdorfin did not antagonize the suppression mediated by the three nucleoside reverse transcriptase inhibitors. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity.
Lee
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TT
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Kashiwada
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Y
Huang
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Snider
J
J
Cosentino
M
M
Lee
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KH
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D016655:HIV Core Protein p24 / Q000032:analysis / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015394:Molecular Structure; D009705:Nucleosides / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D003374:Coumarins; D016655:HIV Core Protein p24; D009705:Nucleosides; C094037:suksdorfin