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

Abstract

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.

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

“…Analyzing inclusion complexes spectra from MA and CO samples, there is an O–H axial deformation characterized by a narrow absorption band around 3500–3000 cm −1 . Changes in intensity at this broad peak was associated with inclusion complex formation towards lower wavenumbers and decrease in intensity and broadening, upon complexation [ 46 ]. Also, a significant reduction in the POH characteristic absorption bands occurs probably due to a vibration restriction following the complexation process.…”

Volatile Nitrogenous Compounds from Bacteria: Source of Novel Bioactive Compounds

“…The nanoencapsulation or complexation with cyclodextrins have been exploited to improve bioavailability of drugs and their specificity to the site of action. We have recently proposed an inclusion complex of isopentyl caffeate in β‐cyclodextrin (β‐CD) [89] . Molecular docking was used to evaluate the interactions between the drug and β‐cyclodextrin, and we demonstrated a greater solubility of the complex compared to ICaf alone, and its effectiveness against L. amazonensis and L. chagasi in vitro.…”

“…Leishmaniasis is an example of a tropical disease, which is caused by protozoan parasites belonging to the genus Leishmania , predominantly affecting African, Asian and Latin American countries [88] . Chemotherapy is its standard treatment, but it is strongly associated with high toxicity and low efficiency with limited patients compliance of such endemic regions and new treatments are thus being proposed [89] . A potent imidazo[1,2‐a]pyrazine‐based antileishmanial compound has been reported by Bazin et al.…”

Exploring Innovative Leishmaniasis Treatment: Drug Targets from Pre‐Clinical to Clinical Findings

“…Our group has been studying isopentyl caffeate (ICaf, S5) for its antileishmanial activity. ICaf is derived from caffeic acid and has shown good activity against the promastigote and amastigote forms of cutaneous ( L. amazonensis ) and visceral ( L. chagasi ) leishmaniasis [34,35] . The hydrophobic nature of ICaf limit its bioavailability.…”