High-Throughput of Indoline Derivatives against Leishmania major and Trypanozoma cruzi

Abstract

Leishmania major and Trypanozoma cruzi are obligate intracellular parasites responsible for Leishmaniasis and Chaga’s disease, respectively. These neglected diseases are endemic in many regions such as Africa and South America, and are becoming a serious problem in the blood and tissue banks in the U.S. due to high immigration of people from endemic regions. Current treatments are characterized by their low efficacy against parasites and high toxicity in humans. Therefore, the discovery of new ways to treat these parasitoses has become urgent. Drug Screening of novel compounds serves as a starting point for the design of new therapies and for understanding the interaction between a drug and its target. In this study, experiments utilizing transgenic L. major strain Friedlin clone V1 (expressing luciferase gene) and T. cruzi Y strain (wild type) were performed testing the viability of these parasites in the presence of Indoline derivatives inhibitors. Additionally, mammalian cells were also incubated with these compounds to test for toxicity. All five compounds displayed toxicity against L. major promastigotes at concentrations between 200 μM to 6.25 μM. Moreover, these compounds were not toxic to the human cell line, U2-OS (osteoblasts), at these concentrations. Currently, experiments are in progress testing the viability of T. cruzi epimastigotes against these compounds