Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers

Citation
P. Imming et al., Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers, INFLAMM RES, 50(7), 2001, pp. 371-374
Citations number
12
Categorie Soggetti
Immunology
Journal title
INFLAMMATION RESEARCH
ISSN journal
10233830 → ACNP
Volume
50
Issue
7
Year of publication
2001
Pages
371 - 374
Database
ISI
SICI code
1023-3830(200107)50:7<371:APC[AE>2.0.ZU;2-R
Abstract
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.