PREPARATION AND ANTITUMOR ACTIVITIES OF BETA-(1-]6) BRANCHED (1-]3)-BETA-D-GLUCAN DERIVATIVES

The formylmethylated and aminoethylated derivatives of schizophyllan ( SPG), a beta-(1-->6)-branched (1-->3)beta-D-glucan from Schizophyllum commune FRIES, were prepared through dimethoxyethylated SPG which was synthesized by the reaction of SPC with dimethylchloracetal under an a lkaline condition. The degree of the substitution of formylmethyl grou ps in the formylmethylated derivative of SPC was estimated as approxim ately 0.19, and the locations of formylmethyl groups in the derivative were predominantly located at O-6 and/or O-4 positions in glucose res idues. The molecular weights of these derivatives were similar to that of SPG, and the helical structure of the derivatives did not seem to he different. The antitumor activities of the formylmethylated and ami noethylated derivatives of SPG against subcutaneously implanted sarcom a 180 solid tumor in mice by intraperitoneal (i.p.) administration R-e re increased more effectively than that of SPG at a dose of 10 mg/kg/d for 7 d starting from 76 after transplantation of sarcoma 180, The ac tivities inducing tumor regressing factor of the formylmethylated and aminoethylated derivatives were 1.5 to 2 times stronger than that of S PG at a dose of 100 mg/kg. Formylmethylated and aminoethylated derivat ives of SPG as well as SPG itself retained the potentiating activity f or the reticuloendothelial system. The productions of soluble cytotoxi c factors secreted from murine macrophages by the administration of th e formylmethylated and aminoethylated derivatives of SPG, which were p robably superoxide anion and tumor necrosis factor as measured by the potency of the nitro blue tetrazolium reduction and the cytotoxic acti vity against L929 cells, respectively, appeared to be more efficient t han that of SPG.