Quantifying Redox Potentials for Artemisinin Resistant (ARTR) Malaria

NIH RePORTER · NIH · R21 · $191,150 · view on reporter.nih.gov ↗

Abstract

"Quantifying Redox Potentials for Artemisinin Resistant (ARTR) Malaria" Capitalizing on recent characterization of coumarin - based fluorescent GSH probes we have synthesized less expensive and more convenient probes 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. We are thus uniquely able 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. Thus, quantifying redox environment of the DV, where FPIX is released during Hb catabolism, is essential for testing particularly attractive hypotheses for ART drug pharmacology and resistance.

Key facts

NIH application ID
10606620
Project number
5R21AI168720-02
Recipient
GEORGETOWN UNIVERSITY
Principal Investigator
PAUL D. ROEPE
Activity code
R21
Funding institute
NIH
Fiscal year
2023
Award amount
$191,150
Award type
5
Project period
2022-04-08 → 2025-03-31