Theoretical Study of Angiotensin Receptor Blockers Losartan Candesartan and Olmesartan and Their Suggested Metabolites

Abstract

The activity of most Angiotensin Receptor Blockers (ARBs) is associated with the stability of their metabolites via a process termed bioactivation. A process called biotransformation forms these stable metabolites. The reactivity of these metabolite intermediates makes it difficult to observe and describe them directly. This work employed computational chemistry to investigate certain (ARBs) and their metabolites, as well as to forecast the most stable parent drugs. Homo values show that the (Losa.M) metabolite product is the lowest energy value for the Homo values, the thermodynamic energy, and the zero-point energy, in addition to having the lowest value of entropy associated with the rest of the other compounds. Losa. metabolism or biotransformation occurred via the oxidation of methanol moiety at position 5 of imidazole heterocyclic ring which produces the more stable carboxylic acid metabolite Losa M., this chemical reaction does not occur in the case of Olme and Cande. Olme and Cande undergo metabolism in another mechanism which is ester hydrolysis process, this reaction occurs rapidly and completely by GI esterases, the HOMO of these two drugs has low energy, (their HOMOs are not filled), and they are highly susceptible to reduction. and thus, this potential hydrolysis increased the drug metabolism and thus excretion.