In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches.

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Chagas and leishmaniasis are two neglected diseases considered as public health problems worldwide, for which there is no effective, low-cost, and low-toxicity treatment for the host. Naphthoquinones are ligands with redox properties involved in oxidative biological processes with a wide variety of activities, including antiparasitic. In this work, in silico methods of quantitative structure–activity relationship (QSAR), molecular docking, and calculation of ADME (absorption, distribution, metabolism, and excretion) properties were used to evaluate naphthoquinone derivatives with unknown antiprotozoal activity. QSAR models were developed for predicting antiparasitic activity against Trypanosoma cruzi, Leishmania amazonensis, and Leishmania infatum, as well as the QSAR model for toxicity activity. Most of the evaluated ligands presented high antiparasitic activity. According to the docking results, the family of triazole derivatives presented the best affinity with the different macromolecular targets. The ADME results showed that most of the evaluated compounds present adequate conditions to be administered orally. Naphthoquinone derivatives show good biological activity results, depending on the substituents attached to the quinone ring, and perhaps the potential to be converted into drugs or starting molecules.