Synthesis of Oxazoloquinolone Derivatives and Evaluation of Their Potency to Reactivate Rat Brain Acetylcholinesterase Inhibited by Chlorpyrifos

Nowadays organophosphorous (OP) poisoning is one of the most common causes of toxicity throughout the world. Two functionally different types of drugs are used in common to treat such intoxication cases. The first type includes the reactivators of acetylcholinesterase (AChE)- oximes, which have the capability to restore the physiological function of inhibited AChE. The second type includes anticholinergics, such as atropine, which antagonize the effects of excessive ACh by blocking of muscarinic receptors. Alternatively, anticholinergics and reactivators may be co-administered to get synergistic effects. At muscarinic and nicotinic synapses, organophosphorous compounds inhibit AChE release by phosphorylation at enzyme’s active site. AChE regenerative process can be accelerated by detaching the OP at -OH group of the enzyme. OP compound combines with AChE enzyme forming a complex making it inactive. After ageing of the inactive state of AChE, it is difficult to break the complex to regenerate the enzyme resulting in acetylcholine accumulation at synapses.