# Discovery  of Antimalarials with Novel Mechanism of Action

> **NIH NIH R01** · UNIVERSITY OF CENTRAL FLORIDA · 2020 · $370,564

## Abstract

Malaria still afflicts about half of the world population causing about 500,000 deaths, mostly
children. The global economic toll of malaria is enormous. Most of the drugs that are currently
utilized for malaria treatment are losing their effectiveness due to widespread emergence of
drug resistance. Even artemisinin-based combination treatments (ACTs) that are the front-line
therapies against falciparum malaria are showing signs of resistance in endemic regions of
Southeast Asia. Therefore, it is urgent to identify new drug leads acting on novel targets for the
development of next generation of therapies against malaria. We have screened
cheminformatics-selected 2,115 unique scaffolds from a BioDesign library that incorporates
privileged features of pharmacologically relevant natural products for antiplasmodial activities.
This screen has identified two scaffolds that exhibit potent antiplasmodial activity, acting early
on parasite's asexual life cycle, including invasion. One of the scaffold also possess stage V
gametocyte activity. The proposed research seeks to establish and further develop these novel
antimalarial chemotypes. We hypothesize that these chemotypes will be excellent platforms for
hit-to-lead optimization studies that will yield effective antimalarial lead compounds targeting
cellular mechanisms distinct from current malaria drugs. To accomplish the objective of
developing new malaria therapeutics and prove our hypothesis, we plan to: (a) Design and
synthesize early-acting lead compounds through structure-activity and structure-property
relationship studies. (b) Determine stage-specific action, resistance profile, pharmacological
properties, in vivo pharmacokinetics, toxicology, transmission blocking activity, and antimalarial
efficacy. (c) Determine molecular targets of the scaffolds by whole genome sequencing of
resistant lines and chemical proteomics. The proposed research is highly significant because at
the end of the project we expect to have novel antimalarial lead compounds with defined
mechanism of action.

## Key facts

- **NIH application ID:** 9841370
- **Project number:** 5R01AI131398-03
- **Recipient organization:** UNIVERSITY OF CENTRAL FLORIDA
- **Principal Investigator:** DEBOPAM CHAKRABARTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,564
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841370

## Citation

> US National Institutes of Health, RePORTER application 9841370, Discovery  of Antimalarials with Novel Mechanism of Action (5R01AI131398-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9841370. Licensed CC0.

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