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 (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

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 a 50% inhibitory concentration (IC50) of 0.3mM 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 (10mg/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%).

Original languageEnglish
Article numbere02165-20
JournalAntimicrobial Agents and Chemotherapy
Volume65
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Amastigote
  • Antileishmanial
  • Bioflavonoids
  • Cutaneous leishmaniasis
  • Flavonoids
  • Leishmania
  • Promastigote

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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