# Development of Novel Natural Product Inspired Antileishmanial Drugs

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $189,593

## Abstract

SUMMARY
Leishmania and other kinetoplastid parasites cause devastating diseases that afflict millions of people, yet
current antileishmanial therapies are woefully inadequate, suffering from toxicity, difficulty of delivery,
development of drug resistance, poor efficacy, etc. Hence, there is a widely recognized and urgent need for
development of novel therapies that represent improvements over current drugs. This proposal will explore the
potential of the natural product-derived tambjamines as potential novel drug leads against leishmaniasis.
Tambjamines and structurally related compounds are potent inhibitors of growth of malaria parasites in vivo in
murine models of malaria, with some of them being curative when delivered as a single oral dose. Initial
experiments with 106 structurally diverse pyrrolylpyrromethene alkaloid analogs identified 26 tambjamines with
30-100 nM EC50 values for growth inhibition of Leishmania mexicana and L. donovani amastigotes growing
inside mammalian macrophages and in vitro therapeutic indices >10, making this class of compounds almost 2
orders of magnitude more potent that current antileishmanial drugs and thus promising candidates for
development of new orally bioavailable drugs for use against these parasites. In this proposal, novel
tambjamines will be synthesized with expected improved properties for in vivo efficacy, including superior
metabolic stability, increased aqueous solubility for improved oral bioavailability, and decreased toxicity. In vitro
and in vivo pharmacokinetic properties will be determined for new tambjamines, and the most promising
analogs will be tested for efficacy in controlling both cutaneous leishmaniasis induced by L. mexicana and fatal
visceral leishmaniasis caused by L. donovani in murine models of these diseases. The overall objective is to
advance tambjamines to the level of compounds that are active against Leishmania parasites in vivo so that
they can be further developed as novel, potent, orally bioavailable leads toward new antileishmanial drugs.

## Key facts

- **NIH application ID:** 10382455
- **Project number:** 5R21AI160670-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Scott M Landfear
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $189,593
- **Award type:** 5
- **Project period:** 2021-04-02 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382455

## Citation

> US National Institutes of Health, RePORTER application 10382455, Development of Novel Natural Product Inspired Antileishmanial Drugs (5R21AI160670-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10382455. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*