WF14865A and B, New Cathepsins B and L Inhibitors Produced by Aphanoascus fulvescens

I. Taxonomy, Production, Purification and Biological Properties

Abstract

WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated separately from the culture mycelium of a fungal strain Aphanoascus fulvescens No. 14865. Spectroscopic analysis revealed that both WF 14865A and B were composed of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or leucine. These compounds inhibited human cathepsins B and L with IC₅₀ values in the range of 8.4-72 nM in vitro. Though their in vitro properties were typical as trans-epoxysuccmyl type inhibitors, they exerted strong bone resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2-10mg/kg.