The alkylphospholipid edelfosine shows activity against Strongyloides venezuelensis and induces apoptosis-like cell death

Abstract

Strongyloidiasis is widely distributed in the tropical and subtropical areas. Ivermectin is the drug of choice for the treatment. However, the concerns about relying treatment on a single drug make identification of new molecules a priority. Alkylphospholipid analogues, including edelfosine, are a group of synthetic compounds that have shown activity against some parasites. The objective was to assess the in vitro and in vivo activity of edelfosine, miltefosine, perifosine against Strongyloides venezuelensis. Moreover, apoptosis-like mechanism in larvae after treatment was studied. Edelfosine displayed the highest activity and the best selectivity index (LD50=49.6 ± 5.4μM, SI=1.1) compared to miltefosine or perifosine. Third stage larvae after culture with edelfosine were not able to develop an infection in mice. Treatment of mice with edelfosine showed reduction of 47% in parasitic females allocated in the gut. Moreover, DNA fragmentation was observed by TUNEL staining in larvae treated with edelfosine. These results suggest that edelfosine could be an effective drug against strongyloidiasis, probably through induction of apoptosis-like cell death.

Anticancer Agent Edelfosine Exhibits a High Affinity for Cholesterol and Disorganizes Liquid-Ordered Membrane Structures

“…The capacity of edelfosine to destabilize liquid-ordered domains that has been widely illustrated in a number of previous works (see ref for a review) together with the results presented in this paper support the theory that the antitumor drug edelfosine acts through reorganization and modification of lipid rafts in liquid-ordered state (L o ). This conclusion supports that these domains are a promising therapeutic target against cancer and against parasites as Leishmania donovani and Stronglioides venezuelensis …”

“…In this way, they may interfere with normal lipid metabolism, lipid-dependent transduction mechanisms, and membrane structure and dynamics. These actions may explain their antitumor activity , and also their activity against parasites. , In the case of the antitumor activity, it is interesting that they act through selective apoptosis of tumor cells but they do not interfere with the normal ones. , …”

“…These actions may explain their antitumor activity 1,2 and also their activity against parasites. 3,4 In the case of the antitumor activity, it is interesting that they act through selective apoptosis of tumor cells but they do not interfere with the normal ones. 5,6 The first discovered compound, which is already being used as anticancer drug, of this family is edelfosine, EDF (ET-18-O-CH 3 , 1-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine) (see Figure 1).…”

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer

“…Edelfosine shows a higher antileishmanial activity than miltefosine [175,176]. Edelfosine also shows additional antiparasitic activities, including anti-Schistosoma mansoni [177,178] and anti-Strongyloides venezuelensis [179] activities. When it comes to cancer, and despite new generations of APLs having been synthesized, edelfosine shows the highest antitumor activity against a wide number of different hematological and solid tumors [132,135,146,170,180].…”

Berberina, curcumina y quercetina como potenciales agentes con capacidad antiparasitaria

“…En cuanto a los ensayos con L3 de S. venezuelensis, en una microplaca de 96 pozos se agregaron 100 μl con 150 larvas por pozo las cuales se preincubaron 30 min (28 °C) y finalmente se agregaron 100 μl de los tratamientos previamente descritos. Como control positivo se usó IV (10 μM) y como control negativo agua destilada (Legarda-Ceballos et al, 2016), el ensayo se llevó a cabo durante 72 h a 28 °C y la viabilidad fue evaluada directamente mediante el registro del movimiento larval después de la estimulación con luz natural directa durante dos minutos utilizando un microscopio invertido (CK2, Olympus, Japón), las larvas se consideraron muertas cuando no se detectó movimiento durante al menos dos minutos de examen detallado.…”