ABSTRACT
In search for new anti-varicella zoster virus (VZV) compounds with new mechanism of action, we applied a DNA hybridization assay (dot blot method) for screening. Using this method, we screened microbial products and found the polyether compound CP-44161 from the culture broth of an actinomycete strain. CP-44161 was previously reported as an anticoccidal agent, but there has been no claim of its antiviral activities. CP-44161 showed strong anti-VZV activity against pOka strain by plaque reduction assay. Moreover, CP-44161 showed lower cytotoxicity than other antiviral polyethers, such as monensin and nigericin. Its better safety margin and strong anti-VZV properties make it a good candidate for a new anti-VZV agent.
Subject(s)
Antiviral Agents/pharmacology , Furans/pharmacology , Herpesvirus 3, Human/drug effects , Pyrans/pharmacology , Actinomycetales/chemistry , Actinomycetales/classification , Actinomycetales/metabolism , Bridged-Ring Compounds , Carbohydrate Sequence , Cell Line, Tumor , Cytopathogenic Effect, Viral/drug effects , DNA, Viral/chemistry , DNA, Viral/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Ethers , Fermentation , Humans , Immunoblotting , Indicators and Reagents , Molecular Sequence DataABSTRACT
FR225654, a novel gluconeogenesis inhibitor, was isolated from the culture broth of Phoma sp. No. 00144 and purified by adsorptive resin and reverse-phase column chromatography. This compound is a potent inhibitor of gluconeogenesis and is a promising candidate of anti-diabetic agent.
Subject(s)
Fungi , Gluconeogenesis/drug effects , Hepatocytes/drug effects , Hypoglycemic Agents/isolation & purification , Naphthalenes/isolation & purification , Animals , Cells, Cultured , Fermentation , Hepatocytes/metabolism , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Molecular Structure , Naphthalenes/chemistry , Naphthalenes/pharmacology , RatsABSTRACT
The novel gluconeogenesis inhibitor FR225654, isolated from the culture broth of Phoma sp. No. 00144, has an unique structure that consists of a highly oxygenated trans-decalin ring and a beta-keto-enol, with a characteristic side chain. This compound selectively inhibited gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in several in vivo mouse models.
Subject(s)
Blood Glucose/drug effects , Gluconeogenesis/drug effects , Hepatocytes/drug effects , Hypoglycemic Agents/pharmacology , Naphthalenes/pharmacology , Administration, Oral , Animals , Cells, Cultured , Diabetes Mellitus, Experimental/drug therapy , Hepatocytes/metabolism , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Male , Mice , Mice, Inbred C57BL , Naphthalenes/administration & dosage , Naphthalenes/therapeutic use , RatsABSTRACT
The novel gluconeogenesis inhibitor FR225659 and four related compounds were isolated from the cultured broth of a fungal strain No. 19353. These compounds inhibited the glucagon-stimulated gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in two different in vivo models.
Subject(s)
Gluconeogenesis/drug effects , Hepatocytes , Hyperglycemia/prevention & control , Hypoglycemic Agents/pharmacology , Animals , Cells, Cultured , Female , Hepatocytes/drug effects , Hepatocytes/metabolism , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/therapeutic use , Mice , RatsABSTRACT
FR225659 and four related compounds are novel gluconeogenesis inhibitors that consist of a novel acyl-group and three abnormal amino acids. They were isolated from the culture broth of Helicomyces sp. No. 19353 and can be purified by absorptive resin and reverse-phase column chromatography. They are potent inhibitors of gluconeogenesis in primary cultured rat hepatocytes and thus may be useful as anti-diabetic agents.
