Chemical and enzymatic stability evaluation of lipoamino acid esters of idebenone

Lipophilic conjugates of idebenone (IDE) with short-chain alkylamino acids were previously synthesized and evaluated in vitro for their antioxidant properties. In this study, their susceptibility to chemical and enzymatic hydrolysis was evaluated. Results indicated that these derivatives release the parent drug quantitatively via enzymatic hydrolysis by serum and liver esterases, with a cleavage rate related to the length of the alkyl side chain. Consequently, the present lipoamino acid conjugates of IDE are prodrugs and their in vivo effects are mediated through the parent compound released in the body.