Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers.
OBJECTIVE
To elucidate if the planar chiral paracyclophane moiety conveys pharmacological activity to arylacetic acid analogs in two animal models.


METHODS
Female NMRI mice (6 mice/group); female Wistar rats (8 rats/group); thrombocytes from human blood.


METHODS
The enantiomers of [2.2]paracyclophaneacetic acid were applied locally (10(-7) and 10(-6) mol/ear) and orally (10-100 mg/kg).


METHODS
(a) Phorbol myristyl acetate model of acute inflammation of the inner auricle. (b) Oxazolone model of allergic contact dermatitis. (c) Carrageenan model of acute inflammation. (d) Inhibition of cyclooxygenase-1 and 12-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 microM.


CONCLUSIONS
The easily accessible [2.2]paracyclophane moiety should find its use in medicinal chemistry as it is a pharmacophoric substituent with the interesting feature of planar chirality.
Imming
P
P
Institut für Pharmazeutische Chemie der Philipps-Universität, Marburg, Germany. Imming@mailer.uni-marburg.de
Graf
M
M
Tries
S
S
Hirschelmann
R
R
Krause
E
E
Pawlitzki
G
G
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D008968:Molecular Conformation; D010081:Oxazolone; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate
C445900:(2.2)paracyclophaneacetic acid; D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011083:Polycyclic Compounds; D010081:Oxazolone; D002351:Carrageenan; D013755:Tetradecanoylphorbol Acetate