Antitumor activity of tetrahydro-2-furanyl- and tetrahydro-2-pyranyl-glucans obtained by chemical modification of (1 leads to 3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 and its lower molecular weight glucans.
The well-defined (1 leads to 3)-beta-D-glucan with DP (degree of polymerization) 540 and the various chain-length (1 leads to 3)-beta-D-glucans prepared by its hydrolysis were chemically modified to furanyl- and pyranyl-derivatives. As a primary screening, the effect of 20 derivatives thus obtained was tested on Sarcoma 180 solid tumor transplanted sc into allogeneic ICR mice; the dose was 10 mg/kg ip for 10 days. Eleven derivatives that showed a strong antitumor effect on Sarcoma 180 were also tested on Meth-A solid tumor in syngeneic mice. Of the derivatives tested, five furanyl-derivatives (F-4, F-6, F-7, F-10, and F-11) and one pyranyl-derivative (P-5) had potent antitumor effects on this syngeneic tumor system at ip doses of 10 or 30 mg/kg for 10 days. By oral administration, only two derivatives (F-10 and P-3) showed moderate antitumor activity against Sarcoma 180, without complete tumor regression. The mechanism of action of these derivatives was considered to be host-mediated and similar to that of the original glucan, because of a lack of effect in vitro.
D000421:Alcaligenes; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D005663:Furans / Q000627:therapeutic use*; D005936:Glucans / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D011714:Pyrans / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D005663:Furans; D005936:Glucans; D011714:Pyrans