Assuntos
4-Butirolactona/química , 4-Butirolactona/metabolismo , Aminobenzoatos/química , Aminobenzoatos/metabolismo , Benzoatos/química , Benzoatos/metabolismo , Lactonas/química , Lactonas/metabolismo , Streptomyces/metabolismo , 4-Butirolactona/farmacologia , Aminobenzoatos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Benzoatos/farmacologia , Linhagem Celular Tumoral , Fungos/efeitos dos fármacos , Humanos , Lactonas/farmacologia , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , RatosRESUMO
Quinomycin A and its derivatives were identified as potent antimalarial (Plasmodium falciparum) agents in a screen of the RIKEN NPDepo chemical library. IC50 values of quinomycin A and UK-63,598 were approximately 100 times lower than that of the antimalarial drug chloroquine. This activity was mitigated by the addition of plasmid DNA, suggesting that these compounds act against parasites by intercalating into their DNA.
Assuntos
Antimaláricos/farmacologia , DNA de Protozoário/antagonistas & inibidores , Equinomicina/farmacologia , Substâncias Intercalantes/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Cloroquina/farmacologia , DNA de Protozoário/química , Descoberta de Drogas , Equinomicina/química , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Humanos , Concentração Inibidora 50 , Substâncias Intercalantes/química , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , Plasmídeos/química , Plasmídeos/farmacologia , Plasmodium falciparum/enzimologia , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
Two novel quinomycin derivatives, RK-1355A (1) and B (2), and one known quinomycin derivative, UK-63,598 (3), were isolated from a microbial metabolites fraction library of Streptomyces sp. RK88-1355 based on Natural Products Plot screening. The structural elucidation of 1 and 2 was established through two-dimensional NMR and mass spectrometric measurements. They belong to a class of quinomycin antibiotics family having 3-hydroxyquinaldic acid and a sulfoxide moiety. They are the first examples for natural products as a quinoline type quinomycin having a sulfoxide on the intramolecular cross-linkage. They showed potent antiproliferative activities against various cancer cell lines and they were also found to exhibit moderate antibacterial activity.
