Amine-Linked Flavonoids as Agents Against Cutaneous Leishmaniasis

Chin-Fung Chan; Zhen Liu; Iris L K Wong; Xianliang Zhao; Zaofeng Yang; Jiale Zheng; Marianne M Lee; Michael K Chan; Tak Hang Chan; Larry M C Chow

doi:10.1128/AAC.02165-20

Amine-Linked Flavonoids as Agents Against Cutaneous Leishmaniasis

Antimicrob Agents Chemother. 2023 May 1;65(5):e02165-20. doi: 10.1128/AAC.02165-20. Epub 2021 Mar 8.

Authors

Affiliations

¹ Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
² School of Life Sciences and Center of Novel Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.
³ Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China tak-hang.chan@polyu.edu.hk larry.chow@polyu.edu.hk.
⁴ Department of Chemistry, McGill University, Montreal, Quebec, H3A 2K6 Canada.

Abstract

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 IC₅₀ of 0.3 μM against L. amazonensis, L. tropica and L. braziliensis amastigotes. It was metabolically stable (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 SSG (63%).