A first principles investigation on the electron donor ability of synthetic melatonin derivatives: implications for their antioxidant activity
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The electron donor ability of 37 melatonin (MLT) derivatives was investigated at the LC-ωPBE/6–311+G(d) level of theory, which was chosen based on a benchmark study using the experimental vertical ionization energy of MLT as the reference value. Twenty-three of these derivatives had been already synthesized, while 14 are proposed here for the first time. Those with better electron donor ability were identified using vertical ionization energies and the full electron donor acceptor map, both in aqueous solution. They are expected to have the best antioxidant activity provided that the main reaction mechanism ruling such activity is the electron transfer reaction from the MLT derivatives to free radicals. The drug-likeness of the studied compounds was analyzed using the Lipinski and Ghose rules, as well as the Veber criteria. Their synthetic availability and toxicity were also estimated. Considering the calculated data, altogether, two of the already synthesized compounds are proposed as the best prospects for being tested as oral drugs, with therapeutic uses as antioxidants. In addition, two of the derivatives designed here are proposed as the best candidates to be synthesized and tested for antioxidant activity, with potential to be used as oral drugs. These results might motivate the synthesis of these compounds; thus, their potential role as protectors against oxidative stress—and the associated health issues—could be experimentally tested.
KeywordsDFT Ionization energies Melatonin analogues Oxidative stress Toxicity LogP
The author acknowledge the Laboratorio de Visualización y Cómputo Paralelo at Universidad Autónoma Metropolitana-Iztapalapa for computing time. This work was partially supported by project SEP-CONACyT 167491.
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