Objective and Design: To elucidate if the planar chiral paracyclophane moie
ty conveys pharmacological activity to arylacetic acid analogs in two anima
l models.
Material or Subjects: Female NMRI mice (6 mice/group); female Wistar rats (
8 rats/group); thrombocytes from human blood.
Treatment: The enantiomers of [2.2]paracyclophaneacetic acid were applied l
ocally (10(-7) and 10(-6) mol/ear) and orally (10-100 mg/kg).
Methods: (a) Phorbol myristyl acetate model of acute inflammation of the in
ner auricle. (b) Oxazolone model of allergic contact dermatitis. (c) Carrag
eenan model of acute inflammation. (d) Inhibition of cyclooxygenase-1 and 1
2-lipoxygenase (in vitro).
Results: (a) PMA model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/
ear): 58% inhibition after 24 h (p < 0.05). (b) Oxazolone model: pR-(-)-[2.
2]paracyclophaneacetic acid (10(-6) mmol/ear): 42% inhibition after 24 h (p
< 0.05). (c) Carrageenan model: pR-(-)-[2.2]paracyclophaneacetic acid (10
mg/kg): 31.4% inhibition (paw volume 0.48 +/- 0.13 ml). (d) Cyclooxygenase-
1 and 12-lipoxygenase: no inhibition at concentrations up to 10 muM.
Conclusions: The easily accessible [2.2]paracyclophane moiety should find i
ts use in medicinal chemistry as it is a pharmacophoric substituent with th
e interesting feature of planar chirality.