Document 0681
 DOCN  M9650681
 TI    Synthesis, activity and toxicity of novel macrocyclic ligands against
       HIV-1 in Jurkat and CEM-SS cell lines.
 DT    9605
 AU    Balogh-Nair V; Brathwaite CE; Chen CX; Vargas J Jr; Department of
       Chemistry, City College of New York, CUNY 10031,; USA.
 SO    Cell Mol Biol (Noisy-le-grand). 1995;41 Suppl 1:S9-14. Unique Identifier
       : AIDSLINE MED/96171629
 AB    We have developed versatile synthetic routes that afford metal-free
       macrocycles containing different functionalities in their framework.
       Novel oxaziridine and amide containing macrocycles were synthesized, and
       the metal complexes of the latter were also prepared. A series of
       theophilline and thymidine side-arm containing podands as well as
       macrocycles were obtained employing the same methodology. The primary
       anti-viral tests of these synthetic compounds for anti-HIV-1 activity
       was carried out using the XTT-based cytopathicity assay (CEM-SS cells)
       with AZT as positive control. It was found that the nature of the
       macrocyclic headgroups affected the anti-HIV-1 activity. Heteroatom
       containing macrocyclic headgroups displayed activity in the micromolar
       range. Metal complexation did not enhance the activity and side-arm
       substitution resulted in inactive compounds. Cell viability determined
       in both Jurkat and CEM-SS cells was strongly dependent on the structure
       of the macrocyclic framework. The oxaziridine moieties in the macrocycle
       were highly toxic to CEM-SS and less toxic to Jurkat cell lines, while
       amide containing macrocycles were toxic to neither.
 DE    Antiviral Agents/CHEMISTRY/CHEMICAL SYNTHESIS/*PHARMACOLOGY/  TOXICITY
       Aziridines/CHEMISTRY/CHEMICAL SYNTHESIS/TOXICITY  Benzhydryl
       Compounds/CHEMISTRY/CHEMICAL SYNTHESIS/TOXICITY  Cell Survival/DRUG
       EFFECTS  Comparative Study  Drug Design  Drug Screening  Heterocyclic
       Compounds/CHEMISTRY/CHEMICAL SYNTHESIS/TOXICITY  Human  HIV-1/*DRUG
       EFFECTS  Leukemia, Lymphocytic, Acute/PATHOLOGY  Leukemia, T-Cell,
       Acute/PATHOLOGY  Ligands  Molecular Structure  Structure-Activity
       Relationship  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*DRUG
       EFFECTS/VIROLOGY  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).