RESUMO
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.
Assuntos
Antineoplásicos/isolamento & purificação , Policetídeos/isolamento & purificação , Streptomyces/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , México , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Policetídeos/química , Policetídeos/farmacologia , Microbiologia do Solo , Staphylococcus aureus/efeitos dos fármacosRESUMO
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.