Biological activity of chemically synthesized core sugar linked lipid A analog, heptose-(alpha 1----5)-2-keto-3-deoxyoctonic acid-(alpha 2----6)-2,3-diacyloxyacylglucosamine-4-phosphate

• Published in: International journal of immunopharmacology Vol. 14; no. 2; p. 221
• Main Authors: Shimizu, T, Ohtsuka, Y, Yanagihara, Y, Akamatsu, S, Ikeda, K, Achiwa, K
• Format: Journal Article
• Language: English
• Published: England 01.02.1992
• Subjects: Animals; Antineoplastic Agents - pharmacology; Lipid A - analogs & derivatives; Lipid A - pharmacology; Lipid A - toxicity; Lipopolysaccharides; Male; Mice; Mice, Inbred Strains; Mitogens - pharmacology; Structure-Activity Relationship; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0192-0561
• DOI: 10.1016/0192-0561(92)90034-I

The mitogenicity, lethal toxicity and antitumor activity against Meth A fibrosarcoma and the induction of tumor necrosis factor (TNF) of chemically synthesized compounds designated as A-103, 2,3-diacyloxyacylglucosamine-4-phosphate (GlcN-4-P), and A-503), heptose-(alpha 1---5)-2-keto-3-deoxyoctonic acid (KDO)-linked GlcN-4-P (A-103), were determined. Compound A-103 induced significant incorporation of [3H]thymidine of C57BL/6 mice at 25-100 micrograms/ml, and A-503 showed the highest incorporation of [3H]thymidine at 100 micrograms/ml. The mitogenicity of A-503 exhibited a lower activity than of A-103. Compound A-503 showed no lethality at high doses of 25 and 50 micrograms/mouse in C57BL/6 mice loaded with D-galactosamine, whereas A-103 caused the death of one of three mice at a dose of 50 micrograms/mouse. Although, the two compounds with or without muramyl dipeptide showed weak antitumor activity against Meth A fibrosarcoma in BALB/c mice, but there were no remarkable differences between the compounds on antitumor activity. Peritoneal macrophages, stimulated with A-103 or A-503 caused no production of TNF which induces L929 cell lysis in vitro. These findings indicate that the addition of heptose and KDO to GlcN-4-P seems not to affect mitogenic activity, lethal toxicity, antitumor activity and TNF-production of the GlcN-4-P compound (A-103).