Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat

• Published in: Chemical biology & drug design 2011-09, Vol.78 (3), p.445-453
• Main Authors: Raghubir, Ram, Verma, Rajkumar, Samuel, Sheeba S., Raza, Saman, Haq, Wajahul, Katti, Seturam B.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Brain - drug effects; Brain - pathology; Brain Ischemia - drug therapy; Brain Ischemia - pathology; cerebral ischemia; Drug development; Excitatory Amino Acid Transporter 2 - metabolism; Glutamic acid; Glutamic Acid - metabolism; Glutathione - metabolism; Injuries; Ischemia; Male; Neuroprotection; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - chemistry; Neuroprotective Agents - therapeutic use; Peroxisome proliferator-activated receptors; pharmacophores; pioglitazone; PPAR gamma - agonists; PPAR gamma - metabolism; PPARγ agonist; Rats; Rats, Sprague-Dawley; Reperfusion; rosiglitazone; scaffolds; thiazolidin-4-one; Thiazolidinediones - chemical synthesis; Thiazolidinediones - chemistry; Thiazolidinediones - therapeutic use
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2011.01153.x

Recently, some PPARγ agonists like pioglitazone, rosiglitazone, and other newer thiazolidine‐2, 4‐dione (TZD) derivatives have been shown to be neuroprotective in experimental model of cerebral ischemia/reperfusion (I/R) injury. Replacement of active pharmacophore viz: thiazolidine‐2,4‐dione of these PPARγ agonists with biologically privileged scaffold thiazolidin‐4‐one derivatives have been synthesized and bioevaluated in focal cerebral ischemia model in rats with an aim to ameliorate cerebral ischemic damage. Of 20 synthesized molecules, three of the substituted compounds (2, 6 and 18) have shown significant (p