Conference Agenda
Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).
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Daily Overview |
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CP8.1: Drugs and Drug Resistance 1 - 5 min talks Location: Lecture Theatre 1 Session Chair: Christopher Hart, Griffith University Session Chair: Hannah Smith, Griffith University | |
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Investigating PPCS as a Novel Antimalarial Drug Target in Plasmodium falciparum 1: Australian National University, Australia; 2: George Washington University Malaria caused by Plasmodium falciparum remains a major global health challenge, with increasing resistance to frontline treatments highlighting an urgent need for new antimalarial therapies. The coenzyme A (CoA) biosynthesis pathway of P. falciparum represents a promising antimalarial drug target. Phosphopantothenoylcysteine synthetase (PPCS), the second enzyme in the pathway, is of particular interest due to its role as a flux-control step. To identify inhibitors of PfPPCS, we have screened ~50 compounds initially designed to inhibit the bacterial PPCS. RCS-33 and HDS-44 emerged as promising candidates, with antiplasmodial IC50 values of ~1 µM. Although the activity of the compounds can be somewhat modulated by overexpression of PfPPCS, consistent with them being on target, their mechanism of action remains to be confirmed. We are currently generating RCS-33- and HDS-44-resistant parasites to try and identify the target via whole-genome sequencing of resistant parasites. We will also use an enzyme assay and purified PfPPCS to test directly whether the compounds are able to inhibit PfPPCS activity. | |