Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-۴-ones Derivatives as Selective Cyclooxygenase (COX-۲) Inhibitors

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شناسه ملی سند علمی:

JR_IJBMS-16-12_005

تاریخ نمایه سازی: 4 آبان 1400

Abstract:

  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.      

Keywords:

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

Authors

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

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