Structure-antitumor activity relationship of a D-manno-D-glucan from Microellobosporia grisea: effect of periodate modification on antitumor activity.
An antitumor D-manno-D-glucan from Microellobosporia grisea, an actinomycete, has a tetrasaccharide repeating-unit structure, a single alpha-D-mannosyl group being located at both O-3 and O-6 of every other beta-D-(1 leads to 4)-glucosyl residue. The D-mannosyl groups and D-glucosyl residues of the mannoglucan were polyhydroxylated to various extents by controlled periodate oxidation followed by borohydride reduction. The derivatives (PA mannoglucans) were further subjected to mild hydrolysis with acid, to give partially debranched mannoglucans (PA-H mannoglucans). These derivatives were tested for antitumor activity against Ehrlich carcinoma solid tumor in mice. The PA mannoglucans having degrees of polyhydroxylation of less than approximately 50 and 2% of the D-mannosyl groups and D-glucosyl residues, respectively, showed high antitumor activities, similar to that of the original mannoglucan, whereas further polyhydroxylation resulted in a marked decrease in, or complete loss of, the activity. The PA-H mannoglucans, lacking 5-40% of the D-mannosyl branches, still had potent antitumor activities, comparable to that of the original mannoglucan. On the basis of these results, the relationship of the structure of the mannoglucan to the antitumor activity is discussed.
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D005561:Formates / Q000032:analysis; D005936:Glucans / Q000032:analysis* / Q000627:therapeutic use; D008351:Mannans / Q000032:analysis* / Q000627:therapeutic use; D051379:Mice; D010504:Periodic Acid; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005561:Formates; D005936:Glucans; D008351:Mannans; D010504:Periodic Acid; C009288:metaperiodate