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Significant Activity of Pytren-2Q, a 2‑Quinoline Polyamine Compound, against High-Concern Human Pathogenic Fungi
Mario Inclán1,2, Maria Paz Clares1, Eduardo Álvarez-Duarte3
1Molecular Science Institute, Universitat de València, C/Catedrático José Beltrán 2, 46980 Paterna, Spain.
Abstract:
In view of the worldwide expansion of life-threatening invasive fungal diseases (IFDs) and fungal drug resistance, new antifungal drugs are urgently needed. To guide research and public health policies, the World Health Organization (WHO) specified 19 priority-concern human mold and yeast pathogens associated with serious risk of mortality or morbidity. We assessed the in vitro susceptibility of twenty-three fungal pathogens, 13 of them included in the WHO priority concern list, to a set of 24 polyamine derivatives generated by linking either alkylated ethylenediamine or a polyamine macrocycle to heterocycles, such as pyridine or quinoline, or polycyclic aromatic compounds, such as anthracene, pyrene, or fluorene. Here we report strong in vitro antifungal activity of a compound generated by linking 2-quinoline to a pyridinophane macrocycle (Pytren-2Q). Pytren-2Q was particularly active against pathogenic molds including WHO critical priority wild-type and azole-resistant Aspergillus fumigatus. These results, in addition to low toxicity, water solubility, and ease of production of Pytren-2Q, suggest that this compound could be of therapeutic interest and may be worth future investigation and validation.
Insights
New antifungal compounds are crucial due to rising invasive fungal diseases and resistance. A novel compound, Pytren-2Q, shows potent activity against priority fungal pathogens, including azole-resistant Aspergillus fumigatus, suggesting therapeutic potential.
Area of Science:
- Medical Mycology
- Medicinal Chemistry
- Drug Discovery
Background:
- Invasive fungal diseases (IFDs) are a growing global health threat.
- Antifungal drug resistance is increasing, necessitating new therapeutic agents.
- The World Health Organization (WHO) identified 19 priority fungal pathogens.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of novel polyamine derivatives.
- To identify promising candidates for new antifungal drug development.
- To assess compounds against WHO priority fungal pathogens.
Main Methods:
- Synthesized 24 polyamine derivatives.
- Tested in vitro susceptibility of 23 fungal pathogens, including 13 WHO priority species.
- Evaluated activity against wild-type and azole-resistant Aspergillus fumigatus.
Main Results:
- A compound, Pytren-2Q (2-quinoline linked to a pyridinophane macrocycle), demonstrated strong in vitro antifungal activity.
- Pytren-2Q was particularly effective against pathogenic molds.
- High activity was observed against azole-resistant Aspergillus fumigatus strains.
Conclusions:
- Pytren-2Q exhibits significant potential as a novel antifungal agent.
- Its low toxicity, water solubility, and ease of production support further investigation.
- Pytren-2Q warrants future research for therapeutic validation against critical fungal infections.
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