ピトレン-2Q（2-キノリンポリアミン化合物）の懸念の高いヒト病原性真菌に対する顕著な活性

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.