OBJECTIVES: The present study was designed to elucidate the mechanism of tafenoquine uptake in Leishmania and its sterol dependence. METHODS: Because tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and to evaluate the effect of temperature, energy and H+ gradient on drug entry. The influence of sterols on tafenoquine uptake in Leishmania parasites was determined in experiments using sterol-depleting agents such as methyl-β-cyclodextrin or cholesterol oxidase. RESULTS: Tafenoquine exhibited fast entry kinetics into Leishmania in an energy-independent, but pH- and temperature-dependent, non-saturable process. Furthermore, sterol depletion decreased tafenoquine uptake. CONCLUSIONS: These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake.
OBJECTIVES: The present study was designed to elucidate the mechanism of tafenoquine uptake in Leishmania and its sterol dependence. METHODS: Because tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and to evaluate the effect of temperature, energy and H+ gradient on drug entry. The influence of sterols on tafenoquine uptake in Leishmania parasites was determined in experiments using sterol-depleting agents such as methyl-β-cyclodextrin or cholesterol oxidase. RESULTS:Tafenoquine exhibited fast entry kinetics into Leishmania in an energy-independent, but pH- and temperature-dependent, non-saturable process. Furthermore, sterol depletion decreased tafenoquine uptake. CONCLUSIONS: These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake.
Authors: Maya Berg; Raquel García-Hernández; Bart Cuypers; Manu Vanaerschot; José I Manzano; José A Poveda; José A Ferragut; Santiago Castanys; Jean-Claude Dujardin; Francisco Gamarro Journal: Antimicrob Agents Chemother Date: 2015-02-02 Impact factor: 5.191
Authors: José Ignacio Manzano; Ana Perea-Martínez; Raquel García-Hernández; Eduardo Andrés-León; Laura C Terrón-Camero; José Antonio Poveda; Francisco Gamarro Journal: Front Cell Infect Microbiol Date: 2022-04-29 Impact factor: 6.073
Authors: Sayyed Ibrahim Shah; Fazli Nasir; Nadia Shamshad Malik; Muhammad Alamzeb; Muhammad Abbas; Inayat Ur Rehman; Fazli Khuda; Yasir Shah; Khang Weh Goh; Alam Zeb; Long Chiau Ming Journal: Pharmaceuticals (Basel) Date: 2022-08-15