Mustafa Fethi Şahin

Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolone-3-yl and 2-benzothiazolone-3-yl) acetic acid derivatives

Sixteen (2-benzothiazolone-3-yl and 2-benzoxazolone-3-yl) acetic acid derivatives 5 have been tested for anti-nociceptive and anti-inflammatory activity in this study, 4-[2-(6-Benzoyl-2-benzoxazolone-3-yl)acetyl]morpholine (5c), 4-¿2-[6-(2-chloro-benzoyl)-2-benzoxazolone-3-yl]acetyl¿morpholine (5d), 1-[2-(5-chloro-2-benzoxazolone-3-yl)acetyl]pyrrolidine (5f), methyl (6-methyl-2-benzoxazolone-3-yl)acetate (5k) and N,N-diethyl-2-(2-benzothiazolone-3-yl)acetamide (5m) have shown more potent anti-nociceptive activity than others. Among these compounds, 5c, 5d and 5m have exhibited good anti-inflammatory activity, with 5f, and to a lesser extent, the other molecules displaying some toxic potential.

The in vitro effects of new non-steroidal antiinflammatory compounds on antioxidant system of human erythrocytes.

It has been reported by our group that some benzoxazolone and benzothiazolone derivatives showed significant antinociceptive and anti-inflammatory activity [DOGRUER et al. 1997]. It has been speculated that nonsteroidal anti-inflammatory drugs (NSAIDs) can act as the free radical scavengers and possess antioxidant activity. It is also well documented that oxidative stress can play an important role in the side effects of many xenobiotics including NSAIDs. Therefore, in the present study, the effects of six of the above mentioned benzoxazolone and benzothiazolone derivatives bearing 2-pyridylaminocarbonylmetyl moiety at the position 3 (I) on the antioxidant system-related parameters of human erythrocytes have been investigated. Diclofenac and nimesulid were also tested in the same systems as the control, because they are commonly used as NSAIDs. Our results showed that these compounds made significant changes in the antioxidant system of human erythrocyte.

Synthesis, characterization and preliminary screening of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole and 1-(3-pyridazinyl)-5-arylpyrazole derivatives towards cyclooxygenase inhibition

In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a–f, 6a–f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a–f, 8a–f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 μM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads.

Synthesis and analgesic and anti-inflammatory activity of 6-phenyl/(4-methylphenyl)-3(2H)-pyridazinon-2-propionamide derivatives.

For reducing gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) a variety of 6-phenyl/(4-methylphenyl)-3(2H)-pyridazinon-2-propionamide were synthesized. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. All the new compounds were tested in vivo for their analgesic and anti-inflammatory activities. The analgesic activity of the test compounds was determined by phenylbenzoquinone-induced writhing assay and the anti-inflammatory activity was evaluated by the carrageenan-induced rat paw edema model. 6-Phenyl-3(2H)-pyridazinon-2-yl-[4-(4-fluorophenyl)piperazinyl] propanamide IVa-3 was the most active one among the synthesized compounds. Also this compound exhibited most potent anti-inflammatory activity. Acetylsalicylic acid and indometacin were used as reference drugs. Adverse effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with the reference NSAIDs.

Microwave-Assisted Synthesis of 1,3-Benzothiazol-2(3H)-one Derivatives and Analysis of Their Antinociceptive Activity

A rapid and efficient method was developed for synthesis of 6-acyl-1,3-benzothiazol-2(3H)-one derivatives under microwave irradiation (MWI) conditions. The reaction times were shortened compared to conventional heating. Additionally, we synthesized acetic acid and acetamide derivatives of 1,3-benzothiazol-2(3H)-one, 6-acyl-1,3-benzothiazol-2(3H)-one, 5-chloro-1,3-benzothiazol-2(3H)-one and 6-acyl-5-chloro-1,3-benzothiazol-2(3H)-one with the microwave-assisted method and analyzed their antinociceptive activity with the tail flick, tail clip, hot plate and writhing tests. Among the synthesized compounds, 3-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-1,3-benzothiazol-2(3H)-one (6a), 5-chloro-3-{2-oxo-2-[4-(propan-2-yl) piperazin-1-yl]ethyl}-1,3-benzothiazol-2(3H)-one (7e) and 3-[2-(4-butylpiperazin-1-yl)-2-oxoethyl]-5-chloro-1,3-benzothiazol-2(3H)-one (8e) showed significant antinociceptive activity in the tail clip, tail flick, hot plate and writhing tests. Supporting Information available online at http://www.thieme-connect.de/ejournals/toc/amf.

The in vitro hepatic metabolism of 1-phenyl-2-(2-benzothiazolinone-3-yl)ethanone and their reduced derivatives

The in vitro hepatic microsomal metabolism of 1-phenyl-2-(2-benzothiazolinone-3-yl)ethanone (I) and (+/-)-1-Phenyl-2-(2-benzothiazolinone-3-yl)ethanol (II) was studied using both rat microsomal preparations and soluble fractions fortified with NADPH. These two substrates and their potential dealkylation metabolite 2-benzothiazolinone were synthesized and their structures were elucidated by spectral methods. The results showed that (I) was metabolised to (II), the corresponding alcohol by reduction. More alcohol metabolite was observed with microsomes than those obtained with the soluble fractions. No dealkylation of (I) was observed in the experiments using both microsomes and soluble fractions. (II) was metabolised to (I), the corresponding ketone by oxidation. However, compared to the metabolism of (I), more ketone metabolite was observed with soluble fractions than microsomes. (II) was also dealkylated to (III) with only soluble fractions but no dealkylated metabolites were found in the microsomes. In addition, a common unknown metabolite was observed with each substrates.

Traditional Techniques Applied in Olive Oil Production Results in Lower Quality Products in Northern Cyprus

Objectives: Olive oil production and its consumption is one of the traditional characteristics of Northern Cyprus. To date, no research has been conducted to analyze the quality of traditionally produced olive oil. Therefore, within this study, we aimed to analyze the olive oil produced within the island concomitant to the determination and comparison of its quality indices. Materials and Methods: The standard olive oil analysis techniques acknowledged by the IOOC and ISO were employed. Accordingly, the fatty acid content, peroxide level, total phenol content, the levels of carotenoids and chlorophyll, as well as status of oxidation were all tested concomitant to statistical analysis. Results: In contrast to the regional belief and consideration, the results indicated that the olive oil produced locally is highly exposed to oxidation and therefore, it is of lower quality according to the ISO guidelines. Conclusion: The traditional techniques employed for the production, distribution, and storage of olive oil within Northern Cyprus must be re-evaluated and controlled to satisfy the current standards required and employed globally.