ABSTRACT
Coculture of the fungus Fusarium pallidoroseum with the bacterium Saccharopolyspora erythraea was found to produce three new decalin-type tetramic acid analogues related to equisetin. The structures were determined by spectroscopic methods. The absolute configurations were established by circular dichroism spectroscopy and comparing the data with those of equisetin.
Subject(s)
Fusarium/chemistry , Pyrrolidinones/chemistry , Pyrrolidinones/isolation & purification , Saccharopolyspora/chemistry , Tetrahydronaphthalenes/chemistry , Coculture Techniques , Molecular StructureABSTRACT
Bioactivity-guided fractionation of an extract of Burkholderia thailandensis led to the isolation and identification of a new cytotoxic depsipeptide and its dimer. Both compounds potently inhibited the function of histone deacetylases 1 and 4. The monomer, spiruchostatin C (2), was tested side by side with the clinical depsipeptide FK228 (1, Istodax, romidepsin) in a murine hollow fiber assay consisting of 12 implanted tumor cell lines. Spiruchostatin C (2) showed good activity toward LOX IMVI melanoma cells and NCI-H522 non small cell lung cancer cells. Overall, however, FK228 (1) showed a superior in vivo antitumor profile in comparison to the new compound.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Burkholderia/chemistry , Depsipeptides/isolation & purification , Depsipeptides/pharmacology , Histone Deacetylase Inhibitors/isolation & purification , Histone Deacetylase Inhibitors/pharmacology , Animals , Antineoplastic Agents/chemistry , Depsipeptides/chemistry , Drug Screening Assays, Antitumor , Histone Deacetylase Inhibitors/chemistry , Humans , Mice , Molecular Structure , National Cancer Institute (U.S.) , United StatesABSTRACT
Co-culture of the fungus Aspergillus fumigatus with the bacteria Streptomyces peucetius led to the induction of production of formyl xanthocillin analogues. This mixed fermentation yielded two new metabolites, fumiformamide (1) and N,N'-((1Z,3Z)-1,4-bis(4-methoxyphenyl)buta-1,3-diene-2,3-diyl)diformamide (2), together with two known N-formyl derivatives and the xanthocillin analogue BU-4704. The structures were determined by spectroscopic methods and by comparison with literature. Cytotoxic activity of all the analogues was tested on the NCI-60 cell line screen, and compound 2 exhibited significant activity against several cell lines. The analogues did not show antimicrobial activity.
Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents/isolation & purification , Aspergillus fumigatus/metabolism , Formamides/isolation & purification , Streptomyces/metabolism , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Butadienes/chemistry , Butadienes/isolation & purification , Butadienes/pharmacology , Coculture Techniques , Drug Screening Assays, Antitumor , Fermentation , Formamides/chemistry , Formamides/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Nitriles/chemistry , Nitriles/isolation & purification , Nitriles/pharmacology , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Lithothamnin A (1) is a new bastadin-like metabolite and represents the first report of this class of molecules from the red alga Lithothamnion fragilissimum. Lithothamnin A contains several novel structural features that distinguish it from other bastadins. These unique structural features include novel aromatic substitution patterns and the presence of a meta-meta linkage between aromatic rings, in addition to the meta-para linkage seen in the bastadins. Lithothamnin A is modestly cytotoxic in a panel of six human tumor cell lines.
