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


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.
Cutler
S J
SJ
Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341, USA.
DeWitt Blanton
C
C
Akin
D T
DT
Steinberg
F B
FB
Moore
A B
AB
Lott
J A
JA
Price
T C
TC
May
S W
SW
Pollock
S H
SH
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001554:Benzene / Q000494:pharmacology*; D001920:Bradykinin; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D009097:Multienzyme Complexes; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin
C115293:1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene; D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D012701:Serotonin; D002351:Carrageenan; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D001554:Benzene; D001920:Bradykinin