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 glucagonstimulated gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in two different in vivo models.

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.

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 b -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.

Other bioactive products U 1300The Novel Gluconeogenesis Inhibitor FR225654 that Originates from Phoma sp. No. 00144. Part 1. Taxonomy, Fermentation, Isolation and Physico-Chemical Properties. -Title compound (I) is a potent inhibitor of gluconeogenesis and a promising candidate for an antidiabetic agent. -(OHTSU*, Y.; SASAMURA, H.; TANAKA, M.; TSURUMI, Y.; YOSHIMURA, S.; TAKASE, S.; SHIBATA, T.; HINO, M.; NAKAJIMA, H.; J. Antibiot. 58 (2005) 7, 447-451; Ferment. Res. Lab., Fujisawa Pharm. Co., Ltd., Tsukuba, Ibaraki 300-26, Japan; Eng.) -M. Bohle 02-210

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. The Journal of Antibiotics (2009) Keywords: antiviral; CP-44161; dot blot; polyether; varicella zoster virus INTRODUCTION Varicella zoster virus (VZV) is a member of the Herpesviridae family that causes two distinct clinical syndromes. Primary infection is manifested as varicella (chickenpox). After the primary VZV infection, latent infection is established in the sensory nerve ganglia. Reactivation of latent VZV results in a localized eruption known as herpes zoster (shingles). Herpes zoster develops in approximately 30% of people over a lifetime. The risk of disease increases with age, and also frequently occurs in immunocompromised patients, especially those with human immunodeficiency virus (HIV) infection. Complications of herpes zoster in immunocompetent hosts include postherpetic neuralgia (PHN), encephalitis, myelitis, cranial nerve palsies and peripheral nerve palsies. PHN, a persistent pain syndrome occurring after the resolution of the zoster rash, is the most challenging complication. 1 Standard antiviral drugs currently used in the treatment of VZV infections include acyclovir (ACV), valaciclovir (VACV, the oral prodrug of ACV), famciclovir (the oral prodrug of penciclovir) and vidarabine (Ara-A). 2 A live attenuated VZV vaccine was originally developed as the 'chickenpox vaccine' to prevent varicella. Recently, a new VZV vaccine was developed for protection against herpes zoster. 1Despite a number of recent therapeutic advancements, there remains an urgent need to develop a new class of therapy, especially novel anti-VZV agent with a strong potency against VZV and with a