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 activity against parasites that cause cutaneous leishmaniasis, a tropical disease endemic in 80 countries worldwide. The most promising candidate, , was highly active with IC of 0.3 μM against , and amastigotes. It was metabolically stable (39% and 66% of remaining after 30-minute incubation with human and rat liver microsomes respectively). In LV78 cutaneous leishmaniasis mouse model, intralesional injection of (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 SSG (63%).