Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.

Abstract

OBJECTIVE AND DESIGN:

1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain.

MATERIALS AND METHODS:

The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin.

RESULTS:

CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity.

CONCLUSIONS:

CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.

• Authors: S J Cutler, C DeWitt Blanton Jr, D T Akin, F B Steinberg, A B Moore, J A Lott, T C Price, S W May, S H Pollock
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 47 Issue 7 Pg. 316-24 (Jul 1998) ISSN: 1023-3830 [Print] Switzerland
• PMID: 9719496 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene
• Acetates
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors
• Enzyme Inhibitors
• Multienzyme Complexes
• Serotonin
• Carrageenan
• Mixed Function Oxygenases
• peptidylglycine monooxygenase
• Benzene
• Bradykinin

Topics

• Acetates (pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Arthritis, Experimental (drug therapy)
• Benzene (pharmacology)
• Bradykinin
• Carrageenan
• Cyclooxygenase Inhibitors (pharmacology)
• Edema (chemically induced, drug therapy)
• Enzyme Inhibitors (pharmacology)
• Foot (pathology)
• Inflammation (chemically induced, drug therapy)
• Male
• Mice
• Mixed Function Oxygenases (antagonists & inhibitors)
• Multienzyme Complexes
• Pain Measurement (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Serotonin