|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1990 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1989 : ¥1,600,000 (Direct Cost : ¥1,600,000)
During the course of our screening program for novel antitumor antibiotics, we have recently isolated two new pimarane-type antitumor antibiotics named myrocin C and B from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The structures of myrocin C and B were characteriz
ed as a pentacyclic pimarane diterpene composed of a gamma -lactol group and a unique cyclopropane ring on the basis of its physico-chemical properties and spectroscopic data as well as a single-crystal X-ray diffraction analysis of myrocin C monoacetyl derivative, namely 1, 20-cyclo-6, 6, 9-trihydroxy-19-oic-7-oxo-8, 15-pimaradiene-19, 6-gamma -lactone and its 11-oxo derivative. In addition to a related compound named 55-0 substance was isolated from the same metabolite. Mainly, from the comparison of various spectral data between myrocin C, B and 55-0, its structure was proposed as 9-hydroxy7-oxo-1, 5, 8, 15-pimaratetraene-19, 6-gamma -lactone.
From the other fungus, new active substances, a chlorine-containing shikimate-related metabolite and 3-methoxy-2, 5-toluquinine, were isolated from soil collected near Sakai City. The structure including absolute stereochemistry of the chlorine-containing metabolite was established by spectroscopic and X-ray crystallographic studies as (1R, 6R, 9S, 10S)-9-chloro-10-hydroxy-8-methoxycarbony1-4-methylene-2, 5-di-oxabicyclo[4.4.0] dec-3-one-7-ene.
These antibiotics were effective against some Gram-positive bacteria, fungi and yeasts. It is particularly noteworthy that myrocin B and C had a good therapeutic effect on mice infected with Ehrlich ascites carcinoma, with the prolongation rate (T/C) of 169% at a dose of 2.4 m g/kg being significantly higher that than of myrocin C (130%). Cytotoxic effect of chlorine-containing metabolite against murine lymphocytic leukemia P-388 cells is a comparable effect to that obtained for 5-fluorouracil.