Abstract
1-(Benzo[d]thiazol-2-yl)-3-(substituted aryl)urea derivatives were designed and synthesized as our efforts to discover novel anti-Parkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative stress in mice. All of the compounds were found to be active in alleviating haloperidol-induced catalepsy in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of 2-chloro,5-trifluoromethyl-substituted analog, halogen-substituted derivatives exhibited moderate anti-Parkinsonian activity. Biochemical estimations of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) from brain homogenate were carried out to highlight the neuroprotective properties associated with them. Molecular docking studies of these compounds with adenosine A(2A) receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human A(2A) receptor for the design and development of potent antagonists. Parameters for Lipinski's rule of 5 were calculated computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties of a compound. None of the synthesized compounds violated Lipinski's rule, making them suitable drug candidate for the treatment of Parkinson's disease.