Pharmacological Properties of a New Anti-Inflammatory Compound, α-(3,5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), and Its Inhibitory Effects on Prostaglandin Synthetase and 5-Lipoxygenase

Hidaka, T; Hosoe, Kazunori; Ariki, Yutaka; Takeo, Kazuyuki; Yamashita, Toshiaki; Katsumi, Ikuo; Kondo, Hideo; Yamashita, Katsuji; Watanabe, Kiyoshi

doi:10.1254/jjp.36.77

Cited by 33 publications

(14 citation statements)

References 18 publications

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“…This was unexpected because the analgesic potency of known NSAIDs, including indomethacin, in adjuvant-induced pain has been shown to parallel their known anti-inflammatory activity (Kuzuna & Kawai 1975;Winter et al 1979). The difference between analgesic and anti-inflammatory doses for starved rats after a single dose, its potency being weaker than indomethacin and naproxen but slightly stronger than ibuprofen (Hidaka et al 1984). In the present study, when the drug was given orally once a day for 12 days, KME-4 induced intestinal irritation or death resulting from intestinal perforation in rats, but its toxicity was lower than that of indomethacin, naproxen or ibuprofen.…”

Section: On Day 13contrasting

confidence: 51%

Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage

Hidaka

Hosoe

Yamashita

et al. 1986

Journal of Pharmacy and Pharmacology

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alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), an anti-inflammatory drug, possesses analgesic activity in rat models. In the acetic acid-induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8, 7.0 and 18.6 mg kg-1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg-1 day-1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg-1 day-1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.

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Section: On Day 13contrasting

confidence: 51%

Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage

Hidaka

Hosoe

Yamashita

et al. 1986

Journal of Pharmacy and Pharmacology

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“…49 (II), 1006−1011 (1999) hydroxybenzylidene)-γ-butyrolactone (2) (KME-4) [4,5] have been reported as dual inhibitors of prostaglandin and leukotriene synthesis.…”

Section: Synthese Und Untersuchung Der Antiinflammatorischen Aktivitämentioning

confidence: 99%

Synthesis and Evaluation of Anti-Inflammatory Activity of Some Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and Their Michael Addition Products

Tozkoparan

Ga²,

Ertan³

et al. 2011

Arzneimittelforschung

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Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (4-10) were obtained in a one step synthesis by heating 3-aryl-5-mercapto-1,2,4-triazoles (3a-d) with chloroacetic acid and appropriate aromatic aldehyde in acetic acid and acetic anhydride in the presence of anhydrous NaOAc. Michael type addition of cyclic secondary amines (N-methylpiperazine, piperidine) to 4-10 gave 2-phenyl-6-(alpha-aminoarylmethyl)thiazolo[3,2-b]-1,2,4-triazole-5 -ols (4a-10b). The structures of the compounds were confirmed by spectral and elementary analysis. The compounds synthesized in previous and present studies were investigated for their anti-inflammatory activities.

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“…Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly prescribed in drug therapy for inflammatory diseases such as Alzheimer's disease (AD) (McGeer et al ., 1996; Stewart et al ., 1997). Currently available NSAIDs have dual inhibitory activities against cyclo‐oxygenase (COX) and 5‐lipoxygenase (5‐LO) (Vane & Botting, 1998; Hidaka et al ., 1984; Ikuta et al ., 1987). COX is classified into two distinct isoforms, a constitutive form, COX‐1, and a mitogen‐inducible form, COX‐2.…”

Section: Introductionmentioning

confidence: 99%

Effects of S‐2474, a novel nonsteroidal anti‐inflammatory drug, on amyloid β protein‐induced neuronal cell death

Yagami

Asakura

Sakaeda

et al. 2001

British J Pharmacology

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1 The accumulation of amyloid b protein (Ab) in the brain is a characteristic feature of Alzheimer's disease (AD). Clinical trials of AD patients with nonsteroidal anti-in¯ammatory drugs (NSAIDs) indicate a clinical bene®t. NSAIDs are presumed to act by suppressing inhibiting chronic in¯ammation in the brain of AD patients. 2 In the present study, we investigated eects of S-2474 on Ab-induced cell death in primary cultures of rat cortical neurons. S-2474 is a novel NSAID, which inhibits cyclo-oxygenase-2 (COX-2) and contains the di-tert-butylphenol antioxidant moiety. 3 S-2474 signi®cantly prevented neurons from Ab(25 ± 35)-and Ab(1 ± 40)-induced cell death. S-2474 ameliorated Ab-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA completely. 4 Prior to cell death, Ab(25 ± 35) generated prostaglandin D 2 (PGD 2 ) and free radicals from neurons. PGD 2 is a product of cyclo-oxygenase (COX), and caused neuronal cell death. 5 S-2474 signi®cantly inhibited the Ab(25 ± 35)-induced generation of PGD 2 and free radicals. 6 The present cortical cultures contained little non-neuronal cells, indicating that S-2474 aected neuronal survival directly, but not indirectly via non-neuronal cells. Both an inhibitory eect of COX-2 and an antioxidant eect might contribute to the neuroprotective eects of S-2474. 7 In conclusion, S-2474 exhibits protective eects against neurotoxicity of Ab. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for AD via ameliorating degeneration in neurons as well as suppressing chronic in¯ammation in non-neuronal cells.

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Pharmacological Properties of a New Anti-Inflammatory Compound, α-(3,5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), and Its Inhibitory Effects on Prostaglandin Synthetase and 5-Lipoxygenase

Cited by 33 publications

References 18 publications

Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage

Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage

Synthesis and Evaluation of Anti-Inflammatory Activity of Some Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and Their Michael Addition Products

Effects of S‐2474, a novel nonsteroidal anti‐inflammatory drug, on amyloid β protein‐induced neuronal cell death

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