Anilinoquinoline disrupting a network of interconnected parasites

Beyond Malaria: New Compounds Show Promise Against Neglected Tropical Diseases

Theo Raines in Health & Wellness November 2025 • 4 min read.

"Scientists identify potent anilinoquinoline-based inhibitors effective against trypanosomatid parasites, offering a potential multi-disease treatment strategy."

Neglected tropical diseases (NTDs) impact over a billion people globally, causing significant morbidity and mortality. Current treatments often have severe side effects, limited efficacy, and increasing resistance, emphasizing the urgent need for novel chemotherapeutics.

Researchers have been exploring a "parasite hopping" approach, screening compounds effective against one parasite against others responsible for NTDs. This strategy aims to identify broad-spectrum treatments.

A recent study focused on compounds derived from lapatinib, a human tyrosine kinase inhibitor, and found them to be effective against Plasmodium falciparum (malaria). This research expands on those findings, demonstrating the effectiveness of these compounds against Trypanosoma brucei, T. cruzi, and Leishmania spp., which cause human African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. Furthermore, certain compounds showed promising results against animal trypanosomiasis.

Anilinoquinolines: A Multi-Target Solution?

Anilinoquinoline disrupting a network of interconnected parasites

The study focused on a series of anilinoquinoline-based compounds, initially optimized for activity against malaria. These compounds were screened against a panel of trypanosomatid parasites, revealing their broad-spectrum potential.

Key findings include:

Trypanosoma cruzi: Several compounds displayed low micromolar inhibition, with the pyrimidine derivative (14) showing the most potent activity and a high selectivity index.
Leishmania major: Similar SAR trends were observed, with the meta-substituted sulfonamide analog (13) exhibiting the most potent inhibition.
Trypanosoma brucei brucei: Several compounds showed sub-micromolar inhibition, with the pyrimidine derivative (14) demonstrating a 10-fold improvement in potency compared to previous compounds.
Animal Trypanosomiasis: A subset of compounds was active against T. congolense and T. vivax, the causative agents of African animal trypanosomiasis (AAT). Compounds 22 and 23 were more potent than diminazene, a commonly used treatment for AAT.

One promising compound (14) was selected for pharmacokinetic (PK) analysis and demonstrated good brain penetration, a crucial factor for treating stage 2 HAT infections. However, further studies are required to determine why 22, despite good in-vitro results and ADME profile, failed in in-vivo tests. Further optimization is needed to improve ADME profiles and ensure efficacy in vivo.

Future Directions: Towards Broad-Spectrum Therapies

This research identifies a promising series of anilinoquinoline-based compounds with broad-spectrum activity against several neglected tropical diseases.

While further optimization is needed to improve ADME profiles and ensure in vivo efficacy, these compounds represent a significant step towards developing more efficient and accessible treatments for diseases affecting billions worldwide.

Ongoing research is focused on understanding the reasons for the lack of in vivo translation of certain compounds and further optimizing the series as anti-trypanosomal and anti-leishmanial lead compounds.

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This article is based on research published under:

DOI-LINK: 10.1371/journal.pntd.0006834, Alternate LINK

Title: Anilinoquinoline Based Inhibitors Of Trypanosomatid Proliferation

Subject: Infectious Diseases

Journal: PLOS Neglected Tropical Diseases

Publisher: Public Library of Science (PLoS)

Authors: Lori Ferrins, Amrita Sharma, Sarah M. Thomas, Naimee Mehta, Jessey Erath, Scott Tanghe, Susan E. Leed, Ana Rodriguez, Kojo Mensa-Wilmot, Richard J. Sciotti, Kirsten Gillingwater, Michael P. Pollastri

Published: 2018-11-26

Everything You Need To Know

What is the main focus of this research regarding neglected tropical diseases?

The research focuses on anilinoquinoline-based compounds initially developed for malaria, specifically targeting Plasmodium falciparum. These compounds have shown effectiveness against trypanosomatid parasites, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania species, which cause human African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. This “parasite hopping” approach aims to identify broad-spectrum treatments effective against multiple neglected tropical diseases.

Which specific parasites have shown positive responses to the anilinoquinoline compounds, and which compounds were most effective against each?

The compounds have shown activity against several trypanosomatid parasites. For Trypanosoma cruzi, the pyrimidine derivative (14) exhibited potent activity. Against Leishmania major, the meta-substituted sulfonamide analog (13) showed the most potent inhibition. Against Trypanosoma brucei brucei, the pyrimidine derivative (14) demonstrated a significant improvement in potency. Furthermore, certain compounds, like compounds 22 and 23, were active against Trypanosoma congolense and Trypanosoma vivax, which cause African animal trypanosomiasis (AAT), even surpassing the effectiveness of diminazene, a commonly used treatment for AAT.

What did the pharmacokinetic analysis reveal about compound 14, and what challenges were identified with compound 22 during testing?

The pharmacokinetic (PK) analysis of compound 14 revealed good brain penetration, which is a crucial factor for treating stage 2 human African trypanosomiasis (HAT) infections, where the parasites have crossed the blood-brain barrier. However, the study also points out that while compound 22 had good in-vitro results and ADME profile, it failed in in-vivo tests. Further optimization is needed to improve ADME profiles and ensure efficacy in vivo for these compounds.

How do these anilinoquinoline compounds potentially improve upon current treatments for neglected tropical diseases?

The anilinoquinoline compounds address the limitations of current treatments for neglected tropical diseases by offering a potential multi-disease treatment strategy. Unlike existing treatments that often have severe side effects, limited efficacy, and increasing resistance, these compounds show broad-spectrum activity against multiple parasites. This could lead to more efficient and accessible treatments, impacting over a billion people affected by these diseases globally. The “parasite hopping” approach reduces the time and resources required to develop new drugs, because there is a possibility of repurposing existing treatments.

What are the next steps in the research and development of these anilinoquinoline-based compounds?

Future research will focus on further optimization of anilinoquinoline-based compounds to improve their ADME (absorption, distribution, metabolism, and excretion) profiles and ensure efficacy in vivo. Specifically, the unexpected in-vivo failure of compound 22, despite its promising in-vitro results, needs to be investigated. Additional studies are required to determine why 22 failed in in-vivo tests. Broad-spectrum therapies will focus on the further screening of new compounds to identify optimal drug candidates for neglected tropical diseases. The development of these compounds could lead to more effective and accessible treatments for diseases affecting billions worldwide, while providing a means to combat drug resistance.