Open AccessAmine-Linked Flavonoids as Agents against Cutaneous Leishmaniasis
Author(s) -
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
Publication year - 2021
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02165-20
Subject(s) - flavonoid , leishmaniasis , cutaneous leishmaniasis , amine gas treating , in vitro , pharmacology , chemistry , traditional medicine , tropical disease , disease , medicine , biochemistry , immunology , organic chemistry , antioxidant
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 IC 50 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%).