Wantana Reanmongkol and Chalermkiat Songkram

pp. 33 - 40

Abstract

In an attempt to develop selective inhibitors for the cyclooxygenase-2 enzymes as candidates for drugs to treat inflammation and pain, two thiazolidine-2,4-dione analogs were designed and synthesized, (E)-5-(4-isobutylbenzylidene)
thiazolidine-2,4-dione (AW 01) and (E)-5-(2-hydroxybenzylidene)thiazolidine-2,4-dione (AW 05). They were synthesized by
refluxing 4-isobutylbenzaldehyde or 2-hydroxybenzaldehyde, respectively in dried toluene, with thiazolidine-2,4-dione, glacial
acetic acid and piperidine. The anti-inflammatory activities of AW 01 and AW 05 were investigated in a rat model of a
carrageenan-induced paw edema and a croton oil-induced mouse ear edema. The analgesic and antipyretic activities of AW
01 and AW 05 were evaluated using the mouse model of acetic acid-induced writhing and in a rat model using yeast-induced
fever, respectively. Oral administration of AW 01 and AW 05 at a dose of 20 mg/kg significantly inhibited the carrageenaninduced rat paw edema. Administration of AW 01 and AW 05 at the higher dose of 40 and 80 mg/kg, also exhibited a significant reduction of paw edema that was similar to the lower dose of 20 mg/kg. When AW 01 or AW 05 was applied topically
at doses of 0.5, 1.0 and 2.0 mg/ear, it had no significant effect on the mouse ear edema induced by croton oil. An analgesic
activity of AW 01 and AW 05 was observed at a lower dose (10 mg/kg, p.o.) in the acetic acid-induced writhing model. After
administration of AW 01 at a dose of 20, 40 and 80 mg/kg, it significantly reduced writhing, compared with the control group.
A similar result was also observed after administration of AW 05 at the same dosage range as for AW 01. For the antipyretic
activity, AW 01 and AW 05 at the dose of 10 mg/kg, p.o. reduced rat rectal temperature at all time intervals (1-5 h) in the same
way as did the standard drugs. When using AW 01 and AW 05 at the higher dose of 20, 40 and 80 mg/kg, both compounds
significantly reduced pyrexia that was similar to the lower administered dose. Both AW 01 and AW 05 demonstrated a similar
magnitude of anti-inflammatory, analgesic and antipyretic effects. The oral LD50 values of AW 01 and AW 05 were 1631 mg/
kg and greater than 2000 mg/kg, respectively in mice. These results indicate that AW 01 and AW 05, thiazolidine-2,4-dione
analogs, possess systemic anti-inflammatory, analgesic as well as antipyretic potentials but have no topical anti-inflammatory
activity in experimental animal models. 

Keywords

• thiazolidine-2
• 4-dione analogs
• inflammation
• pain
• fever
• experimental animal models