Analysis of the mechanisms of action of isopentenyl caffeate against Leishmania

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Oliveira, SSC (Author) Other; Marques, CSF (Author) Other; de Sousa, DP (Author) Other; Andrade, LN (Author) Other; Fricks, AT (Author) Other; Jain, S (Author) Other; Branquinha, MH (Author) Other; Souto, EB (Author) Other; Santos, ALS (Author) Other; Severino, P (Author) Other

Journal

Title: Biochimie

Vol. 189

Pages: 158-167

ISSN: 0300-9084

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 1 Citation

Other information

Authenticus ID: P-00V-KDK

DOI: 10.1016/j.biochi.2021.06.015

Abstract (EN): Leishmaniasis is a neglected parasitic disease for which the conventional treatment can be considered inefficient and extremely aggressive, generating several and severe side effects. Therefore, the discovery of new drug candidates is important for the improvement in the quality of life of patients. Previously, we reported the promising results of isopentyl caffeate (ICaf) against Leishmania chagasi (agent of visceral leishmaniasis) and Leishmania amazonensis (agent of cutaneous leishmaniasis) promastigotes, displaying IC50 of 1.56 and 1.71 mu M, respectively. Herein, we aimed to decipher the mechanisms of anti-Leishmania action of ICaf. Light and scanning electron microscopy assays showed relevant morphological changes in promastigotes when treated with ICaf, including rounding of the parasite body, shortening of the flagellum, blebs on the plasma membrane and cellular aggregation. The parasite mitochondrion was targeted by ICaf, resulting in a significant reduction in its metabolic activity and electric membrane potential followed by an increase in the production of reactive oxygen species, which culminated in the loss of plasma membrane integrity and parasite death. Relevantly, ICaf also had a potent anti-amastigote action. The IC50 values calculated for intracellular amastigotes of L. amazonensis were 3.27, 1.60 and 1.52 mM, while for L. chagasi the values were 2.48, 1.84 and 1.60 mM, respectively, after treating the infected macrophages with ICaf for 24, 48 and 72 h. ICaf was well tolerated by THP-1 macrophages, which gave rise to excellent selectivity indexes considering both Leishmania species. The current results suggest that ICaf may emerge as a chemotherapeutic alternative for the treatment of leishmaniasis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10