ABSTRACT
Campechic acids A (1) and B (2), two new polyketides, were isolated from the culture extract of Streptomyces sp., and their structures were determined by NMR and MS spectroscopic analysis. Campechic acids are polyether-polyketides functionalized by two tetrahydrofuran rings, an enolized 1,3-diketone, and multiple methyl substitutions. Absolute configuration of nine stereogenic centers in 1, except for four chiral centers in the cyclic ether moieties, was determined by the 1H NMR anisotropy method in combination with chemical degradation. Campechic acids exhibited potent inhibitory effects on tumor cell invasion with IC50 values in the nanomolar to submicromolar range.
Subject(s)
Antineoplastic Agents/isolation & purification , Polyketides/isolation & purification , Streptomyces/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bacillus subtilis/drug effects , Candida albicans/drug effects , Drug Screening Assays, Antitumor , Escherichia coli/drug effects , Humans , Inhibitory Concentration 50 , Mexico , Microbial Sensitivity Tests , Micrococcus luteus/drug effects , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Polyketides/chemistry , Polyketides/pharmacology , Soil Microbiology , Staphylococcus aureus/drug effectsABSTRACT
Abyssomicin I (1), a new modified polycyclic polyketide, was isolated from the culture extract of a soil-derived Streptomyces sp. The structure of 1 was elucidated by interpretation of NMR and other spectroscopic data. The stereochemistry of the new compound was assigned by NOE analysis, chemical derivatization, and application of the modified Mosher method. While 1 was inactive against bacteria and yeasts, the oxidized derivative 7 showed weak activities against gram-positive bacteria. Compounds 1 and 7 exhibited inhibitory effects on tumor cell invasion with IC(50) values of 11 and 0.21 µM, respectively.