HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Biological activities and antitumor effects of synthetic lipid A analog linked N-acylated serine.

Abstract
The mitogenicity, lethal toxicity, production of nitric oxide (NO), induction of tumor necrosis factor (TNF) and antitumor activity against Meth A fibrosarcoma by chemically synthesized N-acylated serine-linked non-phosphorylated (A-606 and A607) and phosphorylated (A-608) acylglucosamine-derived lipid A analog were determined. Compounds A-606, A-608 and A-103 [with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 and C-3 positions] induced significant incorporation of [3H]thymidine into splenocytes of C3H/He mice at concentrations ranging from 3.13 to 50 microM. However, A-607 [with (R)-3-tetradecanoyloxytetradecanoyl and with tetradecanoyl at the C-2 and C-3 positions] showed most significant incorporation of [3H]thymidine. The compounds A-606, A-608 and A-103 did not exhibit the lethality at doses of 30 and 300 nmol/kg in C57BL/6 mice loaded with D-galactosamine, whereas A-607 caused the death of two out of six mice at a dose of 300 nmol/kg. These compounds, except A-607, exhibited little NO production by macrophages, but did cause NO production in the presence of interferon-gamma (IFN-gamma). Peritoneal macrophages, stimulated with A-606-A-608, caused production of TNF which induce L929 cell lysis in vitro, and A-608 showed high production of TNF. NO-inducible activity and induction of TNF by compound A-103 seemed to be lower than that of serine-linked derivatives. A-607, A-608 and A-103 showed antitumor activity against Meth A fibrosarcoma in BALB/c mice, and furthermore, the enhancement of antitumor activity by a combination of A-608 with muramyl dipeptide (MDP) was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsT Shimizu, K Iida, Y Iwamoto, Y Yanagihara, K Ryoyama, T Asahara, K Ikeda, K Achiwa
JournalInternational journal of immunopharmacology (Int J Immunopharmacol) Vol. 17 Issue 5 Pg. 425-31 (May 1995) ISSN: 0192-0561 [Print] England
PMID7591367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Lipid A
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
Topics
  • Animals
  • Antineoplastic Agents (chemistry, pharmacology)
  • Dose-Response Relationship, Immunologic
  • Drug Screening Assays, Antitumor
  • Lipid A (analogs & derivatives, pharmacology, therapeutic use)
  • Lymphocyte Activation
  • Macrophages, Peritoneal (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nitric Oxide (biosynthesis)
  • Sarcoma, Experimental (metabolism)
  • Spleen (metabolism)
  • Tumor Necrosis Factor-alpha (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: