Cyclic polyketide peroxides and acyclic diol analogues from the sponge Plakortis lita.
The sponge Plakortis lita from Papua New Guinea is a source of three cyclic peroxides-ethyl plakortide Z (3), ethyl didehydroplakortide Z (4), and methyl didehydroplakortide Z (5)-and three acyclic diol analogues-ethyl seco-plakortide Z (6), epi-ethyl seco-plakortide Z (7), and ethyl didehydro-seco-plakortide Z (8). The absolute stereochemistry at the three chiral sites of 3 was assigned by preparing 6, which was investigated using the refined Mosher's method. Compounds 4, 5, and 6 were also concluded to have the same absolute stereochemistry as 3. The cyclic peroxides were generally cytotoxic, while the acyclic analogues were devoid of activity. Compound 3 was equally active in vitro against solid tumor and L-1210 leukemia cell lines. Alternatively, 4 was observed in vitro to be moderately solid-tumor selective but did not exhibit in vivo activity against solid tumors in mice.
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
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Harrison
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Crews
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D010545:Peroxides / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010545:Peroxides