Amine-Linked Flavonoids as Agents against Cutaneous Leishmaniasis

We have designed, synthesized, and characterized a library of 38 novel flavonoid compounds linked with amines. Some of these amine-linked flavonoids have potent in vitro activity against parasites that cause cutaneous leishmaniasis, a tropical disease endemic in 80 countries worldwide. The most promising candidate, FM09h, was highly active, with a 50% inhibitory concentration (IC50) of 0.3 mu M against Leishmania amazonensis, L. tropica, and L. braziliensis amastigotes. It was metabolically stable, with 39% and 66% of FM09h remaining after 30-minute incubation with human and rat liver microsomes, respectively. In L. amazonensis LV78 cutaneous leishmaniasis mouse model, intralesional injection of FM09h (10 mg/kg, once every 4 days for 8 times) demonstrated promising effect in reducing the footpad lesion thickness by 72%, displaying an efficacy comparable to that of sodium stibogluconate (SSG) (63%).

Automated summary

A library of 38 novel flavonoid compounds linked with amines were synthesized, with the most promising candidate FM09h showing potent in vitro activity against parasites causing cutaneous leishmaniasis. In a mouse model, intralesional injection of FM09h demonstrated a promising effect in reducing footpad lesion thickness, comparable to sodium stibogluconate.