title: Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmaceutical  Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Adel
authors.initials: SA
authors.lastname: Moallem
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Imenshahidi
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Shahini
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Javan
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Ghandadi
authors.affiliation: Pharmaceutical  Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Etemad
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Vahidehsadat
authors.initials: V
authors.lastname: Motamedshariaty
authors.affiliation: Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Toktam
authors.initials: T
authors.lastname: Hosseini
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
keywords: Anti-Inflammatory; Anticancer; Antinociceptive; COX-2 inhibitor; Celecoxib; Thiazolidin-4-ones