ABSTRACT
The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT(2B) receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays.
Subject(s)
Conus Snail/microbiology , Thiazolidines/isolation & purification , Thiazolidines/pharmacology , Actinobacteria/growth & development , Animals , Calcium/metabolism , Humans , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Philippines , Posterior Horn Cells/drug effects , Posterior Horn Cells/metabolism , Receptor, Serotonin, 5-HT2B/metabolism , Serotonin/metabolism , Streptomyces/chemistry , Streptomyces/growth & development , Thiazolidines/chemistryABSTRACT
Microcionamides A (1) and B (2) have been isolated from the Philippine marine sponge Clathria (Thalysias) abietina. These new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. Their total structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Compound 1 was shown to slowly isomerize about the C-36/C-37 double bond when stored in DMSO. Microcionamides A (1) and B (2) exhibited significant cytotoxicity against the human breast tumor cells lines MCF-7 and SKBR-3 and displayed inhibitory activity against Mycobacterium tuberculosis H(37)Ra.
