1. Inclusion complex of ketoconazole and p-sulfonic acid calix[6]arene improves antileishmanial activity and selectivity against Leishmania amazonensis and Leishmania infantum.
- Author
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de Queiroz VT, Botelho BO, Guedes NA, Cubides-Román DC, Careta FP, Freitas JCC, Cipriano DF, Costa AV, de Fátima Â, and Fernandes SA
- Subjects
- Animals, Mice, Ketoconazole, Macrophages, Mice, Inbred BALB C, Leishmania infantum, Antiprotozoal Agents therapeutic use, Leishmania mexicana
- Abstract
Many previous studies presented the effectiveness of ketoconazole (KTZ) against leishmaniasis. However, the bioavailability and therapeutic efficacy of free KTZ are limited due to its low aqueous solubility. In this study, an inclusion complex (IC6HKTZ) was prepared with p-sulfonic acid calix[6]arene (CX6SO
3 H) to improve the solubility and efficacy of KTZ against Leishmania amazonensis and Leishmania infantum promastigotes. A linear increase in KTZ solubility as a function of CX6SO3 H concentration was verified using the phase-solubility diagram. The resulting diagram was classified as AL -type and a 1:1 host-guest stoichiometry was assumed to prepare IC6HKTZ by freeze-drying. FTIR, TG/DSC, XRD, and solid-state13 C NMR spectroscopy analyses were performed to confirm the formation of IC6HKTZ. The solubility enhancement of KTZ by 120.00 μM CX6SO3 H was about 95 times. The IC50 values of IC6HKTZ and free KTZ were 3.95 and 14.35 μM for Leishmania amazonensis and 6.74 and 17.47 μM for Leishmania infantum, respectively. The viability of DH82 macrophages was not affected by CX6SO3 H. These results show that CX6SO3 H is a new supramolecular carrier system that improves antileishmanial activities to KTZ for the treatment of cutaneous and visceral leishmaniasis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Vagner T. de Queiroz reports financial support was provided by Foundation for Research Support of Espírito Santo. Bianca de O. Botelho reports financial support was provided by Coordination of Higher Education Personnel Improvement. Natalia A. Guedes reports financial support was provided by Coordination of Higher Education Personnel Improvement. Diana C. Cubides-Roman reports financial support was provided by Foundation for Research Support of Espírito Santo. Vagner T. de Queiroz reports a relationship with Federal University of Espirito Santo that includes: employment.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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