β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

Molecules

卷:25

MatheusM. Pereira¹  AndréL. S. Santos²  SimoneS. C. de Oliveira²  MartaH. Branquinha²  ClassiusF. da Silva³  LucianaN. Andrade⁴  DamiãoP. de Sousa⁵  Mayara Castro⁵  ElianaB. Souto⁶  MarcoV. Chaud⁷  Sona Jain⁸  AliniT. Fricks⁸  NathaliaS. Barreto⁸  CarineS. F. Marques⁸  Patricia Severino⁸ 

[1] CICECO-Aveiro Institute of Materials, Departamento f Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;

[2] Departament of General Microbiology, Institute of Microbiology Paulo de Góes, Federal University l Rio de Janeiro, 21941-918 Rio de Janeiro, RJ, Brazil;

[3] Department of Exact Sciences and Earth, Federal University of São Paulo (UNIFESP), 09972-270 Diadema CEP, Brazil;

[4] Department of Medicine, Federal University of Sergipe, CEP 49400-000 Lagarto, Sergipe, Brazil;

[5] Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-900 Paraíba, Brazil;

[6] Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciênciasda Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;

[7] Department of Technological and Environmental Processes, Sorocaba University (UNISO), Rod. Raposo Tavares, Km 92.5, 18023-000 Sorocaba, Brazil;

[8] Postgraduation in Biotechnology Program, Industrial and Institute of Technology and Research (ITP), Tiradentes University (UNIT), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil;

关键词: isopentyl caffeate;    β-cyclodextrin;    inclusion complex;    leishmania;   

DOI  :  10.3390/molecules25184181

来源: DOAJ

【 摘 要 】

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in β-cyclodextrin (β-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:β-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:β-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:β-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:β-CD complex showed an IC₅₀ of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

【 授权许可】

Unknown