# Novel Synergistic Antimalarials with Resistance Reversal Function

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2022 · —

## Abstract

The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. The
devastating situation is largely attributed to and aggravated by the emergence and spread of multidrug-
resistant Plasmodium falciparum, the cause of the deadliest form of malaria. Preventing and delaying
emergence of drug-resistance is an essential goal of antimalarial drug development. Monotherapy and highly
mutable drug targets have each facilitated resistance, and both are undesirable in effective long-term
strategies against multi-drug resistant malaria. The novel chemotype described in this proposal represents a
revolutionary approach. It specifically aims to exploit the strengths of other compounds with ideal traits by
making possible a new combination therapy strategy. Our innovative design addresses an immutable parasite
target and merges intrinsic potency with resistance-counteracting functions in a single molecule. It represents a
novel strategy to expand, enhance, and sustain effective antimalarial drug combinations. Our proposed work in
this application seeks to develop novel, potent, safe, inexpensive, and sustainable antimalarial that can be co-
formulated with other antimalarials in a synergistic combination to treat malaria, thus supporting world-wide
elimination of the disease. The specific goal of this project is to maximize the antimalarial potential of the dual-
function acridone chemotype through structural optimization for potency, synergy, pharmacology and metabolic
stability; to accomplish preclinical assessment of lead candidates that are developed through this program of
research; to evaluate for safety, to investigate the mode of action(s) for these synergistic antimalarial
acridones, and to explore the propensity for drug resistance to selected acridone candidates.

## Key facts

- **NIH application ID:** 10368441
- **Project number:** 1I01BX005674-01A1
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** JANE X KELLY
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368441

## Citation

> US National Institutes of Health, RePORTER application 10368441, Novel Synergistic Antimalarials with Resistance Reversal Function (1I01BX005674-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10368441. Licensed CC0.

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