Comparative in vitro susceptibility of clinical Leishmania isolates to miltefosine and oleylphosphocholine

Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus <i>Leishmania</i>. It poses a significant global health burden, particularly because treatment options are limited. More effective and safer treatments are urgently needed. In previous studies, oleylphosphocholine (OlPC), a novel investigational compound structurally related to miltefosine, exhibited comparable activity to miltefosine in intramacrophage assays across various CL-causing laboratory strains and demonstrated superior efficacy in an experimental CL model. This study investigated the <i>in vitro</i> activity of OlPC against clinical isolates of <i>Leishmania</i> spp., comparing its activity with standard anti-leishmanial drugs, including miltefosine, amphotericin B, and pentavalent antimonial agents. Seventy <i>ex vivo</i> isolates (<i>L. major</i> and <i>L. tropica</i>) obtained directly from CL patients before any treatment were used to capture the diversity of drug susceptibilities in circulating parasite populations. Dose-response curves were fitted using a four-parameter log-logistic model to estimate EC₅₀ and EC₉₀ values. Additionally, a linear mixed-effects model was applied to examine the influence of drug type and species on EC₅₀ values while accounting for within-isolate variability. Our findings indicate that OlPC exhibits potent <i>in vitro</i> anti-leishmanial activity, exceeding that of miltefosine in our <i>in vitro</i> intramacrophage model. To facilitate similar analyses, we provide a dedicated wrapper function in R designed to simplify curve fitting and parameter estimation, making the process more accessible to researchers.