engleski

Determination of antioxidant capacity of pharmacologically active oxime K048

Experimental and clinical experience with organophosphorus (OP) compounds poisoning has directed a numerous research activities concerning physicochemical and therapeutic properties of oximes.Pharmacological actions of oximes are primarily attributed to their ability to reactivate acetylcholinesterase (AChE) inhibited by OP. Since studies have proposed a link between OP poisoning and changes in cellular antioxidant systems, investigations on compounds acting as AChE reactivators with antioxidant properties could be a good approach for OP intoxication treatments. This working hypothesis led us to investigate radical scavenging activity of experimental bispyridinium oxime K048 by using a photometric assay based on the colored radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The DPPH radical quenching capacity was performed for a series of K048 dilutions and compared to the quenching capacity of different concentrations of common antioxidant standards Trolox (vitamin E equivalent) and catechin (polyphenol). The effective relative concentrations (EC50) at which 50% of DPPH has been removed were calculated and corresponded to 12.1 μM for Trolox, 5.3 μM for catechin and 6.08 mM for K048. Although K048 exhibited significantly lower effect in comparison to standard antioxidants, it was capable of donating a hydrogen atom and stabilising the DPPH radical. Observed effect might be attributed to the OH and NH2 groups, which constitute nucleophilic moiety responsible for breaking the bond between the OP inhibitor and AChE. In this context, K048 oxime could be considered as a drug able to act against both AChE inhibition and radical generation.

Organophosphorus compounds; Oximes; K048; Radical quenching

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