Enhancement of nonspecific resistance to bacterial infections and tumor regressions by treatment with synthetic lipid A-subunit analogs. Critical role of N- and 3-O-linked acyl groups in derivatives
| Autor: | Homma Jy, Matsuura M, Akira Hasegawa, Mitsunobu Nakatsuka, Yoshio Kumazawa, Makoto Kiso |
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| Rok vydání: | 1989 |
| Předmět: |
Pharmacology
biology Ratón Stereochemistry Protein subunit Immunology nutritional and metabolic diseases medicine.disease biology.organism_classification Lipid A chemistry.chemical_compound chemistry Biochemistry Glucosamine Pseudomonadales medicine lipids (amino acids peptides and proteins) cardiovascular diseases Binding site Fibrosarcoma hormones hormone substitutes and hormone antagonists Pseudomonadaceae |
| Zdroj: | International Journal of Immunopharmacology. 11:349-358 |
| ISSN: | 0192-0561 |
| Popis: | Enhancement of nonspecific resistance against Pseudomonas aeruginosa infection and regression of growth of Meth A fibrosarcoma by chemically synthesized lipid A-subunit analogs, 4-O- phosphono - D - glucosamine derivatives carrying 3-O- and N-linked acyl groups, were investigated. Compounds carrying an (R)-3-hydroxytetradecanoyl (C14-OH) group at the 2-N-position with (R)-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] or (R)-3-dodecanoyloxytetradecanoyl [C14-O-(C12)] groups at the 3-O-position, termed GLA-60 or GLA-63, respectively, showed strong activity about one-tenth that of natural lipid A. The protective activity of compounds carrying an (R)-3-hexadecanoyloxytetradecanyl group instead of a C14-O-(C14) or C14-O-(C12) group was very weak. GLA-59 carrying the same acyl components as those of GLA-60 but with reversed binding sites showed significant but not so strong protective activity. The activity of compounds possessing a tetradecanoyl group instead of a C14-OH group in GLA-60 or GLA-63 was weaker than that of GLA-60 or GLA-63. Intravenous or intratumoral administration of GLA-59, GLA-60 and GLA-63 induced significant regression of Meth A fibrosarcoma in terms of tumor size, tumor weight and number of cured mice. The activity of GLA-59 was almost equivalent to that of GLA-60. None of the tested compounds exhibited significant pyrogenicity at a dose of 10 μg/kg in rabbits. |
| Databáze: | OpenAIRE |
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