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

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 < 0.001) neuroprotection even much better than rosiglitazone at same dose, when administered 1 h prior to 2/24hrI/R cerebral injury in rats, whereas compounds 10, 15, and 17 also showed significant but moderate effect on most of the parameters used in the study. Moreover, compound 2 and 6 also showed curative potential after 6 h post I/R treatment. The compound 2 has also shown significant effect on glutamate uptake by perhaps enhancing the GLT‐1 activity. Thus, the present study indicates that some of the synthesized thiazolidin‐4‐one substituted PPARγ agonists exhibit better neuroprotection and have potential to ameliorate the ischemic damage. Therefore, this novel class of compounds could be further suitably modified to obtain potent anti‐ischemic agents, warranting clinical exploitation.