Journal of Emerging Trends in Engineering and Applied Sciences: Research Areas

Article Title: Kinetic And In Silico Evaluation Of Levamisole And Albendazole As Rat Hepatic Alkaline Phosphatase Inhibitors
by Abdullahi Z. Lukman, AbdulGaniyu B. Bashir, AbdulRahman A. Salaudeen

Abstract:
Some conditions have been found to be associated with elevated levels of alkaline phosphatase (ALP) in the body, making the inhibition of this enzyme an area of significant interest in medical research. Levamisole has been recognized as an effective inhibitor of alkaline phosphatase, but the inhibitory potential of albendazole and their in silico interaction with alkaline phosphatase have not been fully explored. The aim of this study was to carry out kinetic and in silico evaluation of albendazole and levamisole on the hydrolytic activity of rat hepatic alkaline phosphatase. Spectrophotometric method was used to assay for the enzyme activity in the absence and presence of the drugs. Maximum rate of reaction (Vmax) and Michaelis-Menten constant (Km) were estimated using double reciprocal (Lineweaver-Burke) plots of the specific activity of the enzyme against the substrate concentration. In silico simulations utilized computational tools to predict the binding interactions of levamisole and albendazole with the active site of rat hepatic alkaline phosphatase. The presence of levamisole at 0.1% w/v slightly reduced the Km of the enzyme from 0.824 mM to 0.783 mM while at 0.5% w/v and 1% w/v, the Km of the enzyme increased from 0.824 mM to 1.286 mM and 1.086 mM respectively. The presence of albendazole at 0.1% w/v and 0.5% w/v increased the Km of the enzyme from 0.824 mM to 0.857 mM and 0.885 mM respectively. The docking score, XP GScore and prime energy values of the interaction of levamisole with rat tissue non-specific (hepatic) alkaline phosphatase were -4.422, -4.504, and -20894.02 respectively while the docking score, XP GScore and prime energy values of the interaction of albendazole with rat tissue non-specific alkaline phosphatase were -2.894, -2.978, and 20963.88 respectively. Also, the study revealed that levamisole at 0.1% w/v non competitively inhibited rat hepatic alkaline phosphatase activity while at 0.5% w/v and 1% w/v, inhibited rat hepatic alkaline phosphatase activity by mixed-type mode of inhibition. Also, it was revealed that albendazole at 0.1% w/v non-competitively inhibited rat hepatic alkaline phosphatase activity while at 0.5% w/v, inhibited rat hepatic alkaline phosphatase activity by mixed-type mode of inhibition and at 1% w/v, non-competitively inhibited rat hepatic alkaline phosphatase activity. The in silico evaluation showed that levamisole has a higher inhibitory effect compared to albendazole.This study demonstrates that levamisole is a potent inhibitor of tissue non-specific alkaline phosphatase while albendazole mildly inhibited the enzyme.

Keywords: Alkaline Phosphatase, Insilico, Albendazole, Inhibitors, Enzyme Kinetics

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