# Novel artemisinin derivatives for chemogenomic profiling of Plasmodium falciparum

> **NIH NIH SC3** · UNIVERSITY OF THE INCARNATE WORD · 2022 · $108,549

## Abstract

Malaria, a parasitic mosquito-borne disease, is a major concern worldwide, with 219 million cases occurring in
2017 (WHO 2018 report), causing 435,000 deaths of which 61% were children under 5. Plasmodium
falciparum is the causative agent of the deadliest form of malaria and current treatment guidelines include
artemisinin-based combination therapies (ACTs), combining one artemisinin derivative (artemether, artesunate
or dihydroartemisinin) with one or two different drugs. Most studies have demonstrated that ACTs remain
effective, but partial resistance has been reported in southeast Asia, linked to the development of the parasite’s
ability to remain dormant at the ring stage long enough for clearance of artemisinin-based drugs so the
parasites can re-emerge. Virtually all derivatives of artemisinin currently available are the result of chemical
modifications at “C-10”, or carbon number 10 on its structure (IUPAC numbering). The fungus Cunninghamella
elegans can add a hydroxyl group to carbon number 7 (C7) which, until the use of fungal transformation, was
inaccessible except through extensive and costly total synthesis. The overall objective for this application is to
1) prepare C-7 derivatives of artemisinin linked with hydrophilic groups and fluorescent probes; 2) test those
derivatives against a) standard P. falciparum strains (3D7, W2mef, HB3); b) at least one artemisinin-resistant
phenotype (C2A) and c) test for possible anti-gametocyte action and transmission blocking activity by Standard
Membrane-Feeding Assay; 3) chemogenomic profiling studies of P. falciparum piggyBac single insertion
mutants seeking better understanding of the interaction of these new C7 derivatives of artemisinin with
druggable targets and pathways. The central hypothesis is that derivatives of artemisinin without any steric
hindrance to the peroxide group will allow full interaction with cellular targets, precisely tagging cellular
structures bound to the artemisinin scaffold and enhancing inhibitory effect. These new semi-synthetic
derivatives of artemisinin, built for the first time using functional groups placed structurally on the opposite side
of the peroxide bridge, are expected to have enhanced antimalarial activity, present better pharmacokinetic
profiles and work better as molecular probes for elucidation of mechanisms of action and drug resistance.

## Key facts

- **NIH application ID:** 10643176
- **Project number:** 3SC3GM136576-03S1
- **Recipient organization:** UNIVERSITY OF THE INCARNATE WORD
- **Principal Investigator:** Paulo Batista de Carvalho
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $108,549
- **Award type:** 3
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10643176

## Citation

> US National Institutes of Health, RePORTER application 10643176, Novel artemisinin derivatives for chemogenomic profiling of Plasmodium falciparum (3SC3GM136576-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10643176. Licensed CC0.

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