RESUMO
In the course of screening for inhibitors of the lymphocyte kinase, Lck (p56lck), aiming at novel immunosuppressants, we isolated a novel alkaloid, lymphostin (LK6-A), from the culture broth of Streptomyces sp. KY11783. Lymphostin was produced in a fermentation medium supplemented with a highly porous polymer resin, which prevented the degradation of this compound in the culture broth. Lymphostin inhibited the kinase activity of Lck with an IC50 value of 0.05 microM, and exhibited potent inhibitory activity against the mixed lymphocyte reaction (MLR) with an IC50 value of 0.009 microM.
Assuntos
Imunossupressores/farmacologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/antagonistas & inibidores , Microbiologia do Solo , Streptomyces/metabolismo , Cromatografia Líquida de Alta Pressão , Fermentação , Humanos , Imunossupressores/isolamento & purificação , Testes de Sensibilidade Microbiana , Streptomyces/classificaçãoRESUMO
Lymphostin (LK6-A), a novel immunosuppressant, was isolated from the culture broth of Streptomyces sp. KY11783. Lymphostin showed potent inhibitory activity against the lymphocyte kinase, Lck (p56lck). The structure of lymphostin was determined by spectroscopic methods to be a novel tricyclic aromatic alkaloid. A key feature of the structure is the pyrrolo[4,3,2-de]quinoline moiety which is rare among natural products.
Assuntos
Imunossupressores/química , Pirróis/química , Quinolinas/química , Isótopos de Carbono , Química Farmacêutica , Espectroscopia de Ressonância Magnética , Pirróis/isolamento & purificação , Quinolinas/isolamento & purificaçãoRESUMO
RES-1214-1 and -2, novel and non-peptidic endothelin antagonists, were isolated from the cultured broth of a fungus, Pestalotiopsis sp. RE-1214. RES-1214-1 and -2 selectivity inhibited the ET-1 binding to endothelin type A receptor (ETA receptor) with IC50 values of 1.5 microM and 10 microM, respectively. RES-1214-1 and -2 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in A10 cells. Taxonomy of producing strains, fermentation, isolation, structural determination, and biochemical properties of RES-1214-1 and-2 are described.
Assuntos
Antagonistas dos Receptores de Endotelina , Hidroxibenzoatos/farmacologia , Fungos Mitospóricos/metabolismo , Éteres Fenílicos/farmacologia , Animais , Bovinos , Linhagem Celular , Éteres de Hidroxibenzoatos , Hidroxibenzoatos/química , Estrutura Molecular , Éteres Fenílicos/química , Ensaio Radioligante , Receptor de Endotelina A , Análise EspectralRESUMO
MS-444 is a novel myosin light chain kinase inhibitor, isolated from the culture broth of Micromonospora sp. KY7123. The structure of MS-444 was determined to be 5,8-dihydroxy-3-methyl-(9H)-naphtho[2,3-c]furan-4-one by means of spectral analysis.