Pharmacokinetic Profile of a Drug Repurposing Candidate for the Treatment of Cutaneous Leishmaniasis (in Silico)

Abstract

The calculated or experimental physical-chemical Properties are important for choosing substances that will be used in the treatment of several diseases by different administration routes. Chloroquine, for example, is a drug with several biological activities that has been constantly investigated as an alternative to drug repurposing in different diseases. With respect to leishmaniasis, there are few treatment options, which are invasive and have several adverse effects. Another point is the identification of important drug molecular targets, understand their functions, and thus discovering new therapeutic alternatives. Thus, this work aimed at: performing an in analysis of the pharmacokinetic profile of chloroquine as an option for the treatment of cutaneous leishmaniasis by dermal route; evaluating the interaction of the drug with the enzyme Trypanothione reductase, responsible for the parasite's redox balance. The melting point was obtained in the PUBCHEM database. Analysis showed that chloroquine presented a partition coefficient, molecular weight, and melting point within the established proper range of parameters. The skin permeability coefficient also presented a satisfactory value, as well as the values for total polar surface area, number of rotatable bonds, and sp3 Carbon Fraction. In molecular docking simulations, chloroquine showed interactions with the enzyme TRLb, with a calculated Ki lower than that of the reference compound. This study reinforces the theoretical prediction and good solubility and permeability of chloroquine. The results justify further investigations on the inhibition of TRLb as an important alternative for the treatment of leishmaniasis. HIGHLIGHTS• The theoretical prediction good solubility and permeability of chloroquine;• Chloroquine presents proper physical chemical features for skin permeation;• Chloroquine presented Ki= 4.86 μM against TRLb.