Militarinone A, a Neurotrophic Pyridone Alkaloid from <i>Paecilomyces </i><i>m</i><i>ilitaris</i>¹

A new pyridone alkaloid, militarinone A (1), was isolated by bioassay-guided fractionation from the mycelium of the entomogenous fungus Paecilomyces militaris. Its structure was established by extensive spectroscopic analysis. The compound features an unprecedented side chain and a 1,4-substituted cyclohexyl moiety not previously encountered in microbial metabolites. Militarinone A had a pronounced neurotrophic effect in PC-12 cells at 10 μM concentrations

(+)-<i>N</i>-Deoxymilitarinone A, a Neuritogenic Pyridone Alkaloid from the Insect Pathogenic Fungus <i>Paecilomyces </i><i>f</i><i>arinosus</i>^#

A new pyridone alkaloid, (+)-N-deoxymilitarinone A (1), was isolated from Paecilomyces farinosus RCEF 0097 along with the related metabolites, militarinone D and militarinone B. The sterol 22E,4R-ergosta-7,22-diene-3β,5α,6β,9α-tetraol was also identified. The structures were established by spectroscopic methods, in particular with the aid of extensive NMR experiments. Compound 1 induced neurite sprouting in PC 12 cells when tested at 33 and 100 μM concentrations. A cytotoxic effect was observed in human neurons (IMR-32) at a concentration of 100 μM

Farinosones A−C, Neurotrophic Alkaloidal Metabolites from the Entomogenous Deuteromycete <i>Paecilomyces </i><i>f</i><i>arinosus</i>

Two new yellow pigments, farinosones A (1) and B (2), were isolated from the mycelial extract of the entomogenous fungal strain Paecilomyces farinosus RCEF 0101, together with farinosone C (3), a new metabolite derived from an early step of pyridone alkaloid biosynthesis. The structures were determined by spectroscopic means, in particular by extensive NMR experiments. Compounds 1 and 3 induced neurite outgrowth in the PC-12 cell line at concentrations of 50 μM, while compound 2 was inactive. No cytotoxicity was observed for compounds 1−3 in PC-12 cells when tested at 50 μM concentration in the MTT assay