Laurequinone, a Lead Compound against Leishmania

Abstract

Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of Leishmania amazonensis. Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent.

Acrylonitrile derivatives: In vitro activity and mechanism of cell death induction against Trypanosoma cruzi and Leishmania amazonensis

“…5 μl of JC-1 was added and, after 30 min of incubation, the green (J-monomers, excitation 540 nm/emission 470 nm) and red (J-aggregates, excitation 485 nm/emission 535 nm) fluorescence were measured, and the result were expressed as percentage relative to the negative control of the ratio red/green fluorescence. A positive control was added, carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 100 μM for 3 h) and a reference treatment, miltefosine for L. amazonensis and benznidazole for T. cruzi ( García-Davis et al, 2023 ).…”

Global Health Priority Box: Discovering Flucofuron as a Promising Antikinetoplastid Compound

“…The kit was incubated at 5 µM for 30 min, and the images were captured with the EVOS ® FL Cell Imaging System (ThermoFisher Scientific, Waltham, MA, USA) in the Cy5 light cube (excitation 644 nm/emission 665 nm). Standard treatments were added, including benznidazole for T. cruzi and miltefosine for L. amazonensis and a positive control, hydrogen peroxide (H 2 O 2 ) 600 mM for 30 min [40].…”

Global Remodeling of Host Proteome in Response to Leishmania Infection

“…A recent study explored inhibitors against ATG8 and found increased ROS activity and reduced L. donovani presence in THP1 macrophage cells . Similarly, different anti-leishmanial compounds targeting apoptosis via increased ROS have been also identified recently. − Thus, ATG8-mediated parasite autophagy and apoptosis have become interesting drug targets to test against leishmaniasis.…”