Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues.

Abstract

In order to explore the influence of sulfate groups on the bioactivity profiles of marine alkaloids of the lamellarin class, three such alkaloids, lamellarin alpha, lamellarin alpha 13,20-disulfate and lamellarin H, were synthesized and their activities against HIV-1 integrase and cancer cell lines were compared with those of lamellarin alpha 20-sulfate, which is a selective inhibitor of HIV-1 integrase. Lamellarin alpha does not inhibit HIV-1 integrase but shows moderate cytotoxicity with good cell line selectivity. Lamellarin alpha 13,20-disulfate is a moderate inhibitor of both HIV-1 integrase and cancer cell lines. Lamellarin H is a more potent inhibitor of HIV-1 integrase but lacked the specificity required to be medicinally useful.

• Authors: Christian P Ridley, M Venkata Rami Reddy, Genalyn Rocha, Frederic D Bushman, D John Faulkner
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 10 Issue 10 Pg. 3285-90 (Oct 2002) ISSN: 0968-0896 [Print] England
• PMID: 12150874 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Coumarins
• HIV Integrase Inhibitors
• Heterocyclic Compounds, 4 or More Rings
• Isoquinolines
• Topoisomerase Inhibitors
• lamellarin H
• lamellarin alpha 20-sulfate

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Coumarins (chemical synthesis, pharmacology)
• Drug Screening Assays, Antitumor
• HIV Integrase Inhibitors (chemical synthesis, pharmacology)
• HeLa Cells
• Heterocyclic Compounds, 4 or More Rings (chemical synthesis, pharmacology)
• Humans
• Isoquinolines (chemical synthesis, pharmacology)
• Molluscum contagiosum virus (enzymology)
• Structure-Activity Relationship
• Topoisomerase Inhibitors
• Tumor Cells, Cultured