Synthesis of some urea and thiourea derivatives of naphtha[1,2-d]thiazol-2-amine as anti-Parkinsonian agents that cause neuroprotection against haloperidol-induced oxidative stress in mice

A series of N-(substituted phenyl)-N'-(naphtha[1,2-d]thiazol-2-yl)urea and thiourea derivatives were synthesized starting from N-naphthylthiourea. The structures were confirmed by spectral and elemental analyses. The newly synthesized compounds were found to possess anti-Parkinsonian and antioxidant activities. Anti-Parkinsonian activity was evaluated on haloperidol-induced catalepsy in mice by employing the standard bar test. All of the synthesized compounds ameliorated the catalepsy induced by haloperidol in mice. The most potent compounds (5, 6, 22, and 29) were selected for biochemical evaluation from the brain homogenate and were found to be effective in decreasing the elevated levels of malondialdehyde while restoring the cellular defense mechanisms such as glutathione content as well as glutathione peroxidase and superoxide dismutase activities in haloperidol-treated mice, suggesting the role of free radicals in the pathophysiology of haloperidol-induced catalepsy and possible antioxidant action of title compounds.