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Last Updated: 07/06/2023
Quantifying redox potentials for artemisinin resistant (ARTR) malaria
Objectives
To quantify redox potential of the digestive vacuole, where FPIX is released during Hb catabolism to test if it is essential for ART drug pharmacology and resistance.
Capitalizing on recent characterization of coumarin – based fluorescent GSH probes, less expensive and more convenient probes have been synthesized including interesting morpholino derivatives and dextran conjugates, have characterized their GSH – dependent and other thiol – dependent fluorescence, and in proof – of – principle preliminary experiments have begun to quantify their localization and intensity within the live malarial parasite DV. It has been uniquely possible to quantify DV redox potential for ARTR (artemisinin resistant) vs ARTS (sensitive) parasites and thereby rigorously test, for the first time, the very attractive hypothesis that ferric / ferrous heme ratios may differ for DCP/ARTR parasites. This is an essential issue that further tests the predictions of the widely accepted concept that FPIX heme is the likely “activator” of ART – based drugs. Furthermore, reduced Fe2+PIX / Fe3+PIX would easily explain reduced ART drug potency in ARTR parasites.
Apr 2022 — Mar 2024
$419,760
