Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues.
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.
Ridley
Christian P
CP
Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0212, USA.
Reddy
M Venkata Rami
MV
Rocha
Genalyn
G
Bushman
Frederic D
FD
Faulkner
D John
DJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D008977:Molluscum contagiosum virus / Q000201:enzymology; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003374:Coumarins; D019428:HIV Integrase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; D059003:Topoisomerase Inhibitors; C455555:lamellarin H; C119474:lamellarin alpha 20-sulfate