ABSTRACT
Ophirapstanol trisulfate [1], a new steroid trisulfate related to sokotrasterol trisulfate was isolated from a deep water marine sponge Topsentia ophiraphidites. Compound 1 exhibited significant inhibition in the guanosine diphosphate/G-protein RAS exchange assay. The structure elucidation of 1 and ophirapstanol [2] by nmr spectroscopy is described.
Subject(s)
Mutagens/isolation & purification , Porifera/chemistry , Sterols/isolation & purification , Sulfuric Acid Esters/isolation & purification , Animals , Circular Dichroism , Genes, ras/drug effects , Humans , Magnetic Resonance Spectroscopy , Mutagenicity Tests , Mutagens/toxicity , Sterols/toxicity , Sulfuric Acid Esters/toxicityABSTRACT
A series of analogs of the immunosuppressive lipopeptide microcolin A has been prepared and evaluated for in vitro activity in the human and murine two-way mixed lymphocyte reaction. The compounds tested were obtained by semisynthetic modification and chemical degradation of the natural product. The relative potencies of these analogs suggest that the hydroxyproline and 5-methyl-3-pyrrolin-2-one portion of the molecule are important for immunosuppressive activity and that other structural elements may play an ancillary role. Methanolysis of microcolin A also led to a novel immunosuppressive lactone analog.
Subject(s)
Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Pyrrolidines/chemical synthesis , Pyrrolidines/pharmacology , Amino Acid Sequence , Animals , Humans , Lymphocyte Culture Test, Mixed , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Sequence DataABSTRACT
Three apparent chemotypes of the marine sponge Myrmekioderma styx exist. An acyclic diterpene, styxenol A [1], has been isolated from the shallow water chemotype, while three tricarbocyclic diterpenes 3, 6, and 7 have been isolated from the deep chemotype. The structures were elucidated based on spectral methods including homo- and hetero-nuclear 2D nmr experiments. Compounds 1, 3, and 6 exhibit moderate cytotoxicity against the P-388 murine leukemia cell line and the A549 human lung tumor cell line.
