| چکیده انگلیسی مقاله |
Objective(s): Nowadays, COX- 2 inhibitors such as valdecoxib are removed from the market because of their cardiovascular toxicity and their potential to increase the risk of strokes. In response to this, medicinal chemists have attempted to synthesize new classes of COX-2 Inhibitors. Materials and Methods: In this study, three novel analogues of thiazolidin-4-ones derivatives 2a-c were synthesized. The ability of these compounds to inhibit ovine COX-1 and COX-2 (0.2- 0.8 μM) was determined using a colorimetric method. The cytotoxic effect of the synthesized compounds (25-100 M) was also investigated by measuring their cytotoxicity against Caco-2 and MCF-7 cell lines using MTT assay. Cell apoptosis was determined by flow cytometry. Writhing test (7.5-75 mg/kg) was used to examine the antinociceptive effects in mice. The effect of the analogues against acute inflammation (7.5-75 mg/kg) was also studied using xylene-induced ear edema test in mice. Results: The synthesized compounds showed a weak capacity to inhibit the proliferation of Caco-2 and MCF-7 cell lines. The COX-2 inhibition potency and selectivity index for test compounds 2a–b were as follows; celecoxib > 2b > 2a . On the other hand, all three analogues exhibited strong antinociceptive activity against acetic acid-induced writhing. The anti-inflammatory and antinociceptive effects of the analogues were markedly more than positive control, celecoxib. Conclusion: This study demonstrates that the antinociceptive and anti-inflammatory activity profiles exhibited by the novel synthesized compounds are independent from their COX-2 inhibitory potencies. The found antinociceptive and anti-inflammatory effects can be caused by interaction with other target; independent from COX-2. Accordingly, the compounds 2a-c could serve as lead compounds to develop novel anti-inflammation and antinociceptive drugs. |
| نویسندگان مقاله |
سید عادل معلم | seyed adel moallem
pharmaceutical research center, mashhad university of medical sciences, mashhad, iran 2 medical toxicology research center, mashhad university of medical sciences, mashhad, iran 3 department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
محسن ایمن شهیدی | mohsen imenshahidi
department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
نرگس شاهینی | narges shahini
department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
احمدرضا جوان | ahmad reza javan
department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
محسن کریمی | mohsen karimi
department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
مونا علی بلندی | mona alibolandi
biotechnology research center, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
مرتضی ghandadi | morteza ghandadi
department of pharmacodynamics and toxicology, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
لیلا اعتماد | leila etemad
pharmaceutical research center, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
vahidehsadat معتمدالشریعتی | vahidehsadat motamedshariaty
biotechnology research center, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
تکتم حسینی | toktam hosseini
medical toxicology research center, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
فرزین هادی زاده | farzin hadizadeh
biotechnology research center, mashhad university of medical sciences, mashhad, iran 5 department of medicinal chemistry, school of pharmacy, mashhad university of medical sciences, mashhad, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)
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