Seyed Adel Moallem - Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ۲ Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ۳ Department of Pharmacodynamics and Toxicology, School of Pharmacy,
Mohsen Imenshahidi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Narges Shahini - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Ahmad Reza Javan - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Mohsen Karimi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Mona Alibolandi - Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Morteza Ghandadi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Leila Etemad - Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Vahidehsadat Motamedshariaty - Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Toktam Hosseini - Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Farzin Hadizadeh - Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ۵ Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

  Objective(s): Nowadays, COX- ۲ 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-۲ Inhibitors.   Materials and Methods: In this study, three novel analogues of thiazolidin-۴-ones derivatives ۲a-c were synthesized. The ability of these compounds to inhibit ovine COX-۱ and COX-۲ (۰.۲- ۰.۸ μM) was determined using a colorimetric method. The cytotoxic effect of the synthesized compounds (۲۵-۱۰۰ M) was also investigated by measuring their cytotoxicity against Caco-۲ and MCF-۷ cell lines using MTT assay. Cell apoptosis was determined by flow cytometry. Writhing test (۷.۵-۷۵ mg/kg) was used to examine the antinociceptive effects in mice. The effect of the analogues against acute inflammation (۷.۵-۷۵ 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-۲ and MCF-۷ cell lines. The COX-۲ inhibition potency and selectivity index for test compounds ۲a–b were as follows; celecoxib > ۲b > ۲a . 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-۲ inhibitory potencies. The found antinociceptive and anti-inflammatory effects can be caused by interaction with other target; independent from COX-۲. Accordingly, the compounds ۲a-c could serve as lead compounds to develop novel anti-inflammation and antinociceptive drugs.      

Antinociceptive Anti-Inflammatory Anticancer Celecoxib COX-۲ inhibitor Thiazolidin-۴-ones