Amine-Linked Flavonoids as Agents against Cutaneous Leishmaniasis
| Autor: | Michael K. Chan, Jiale Zheng, Marianne M. Lee, Zhen Liu, Tak Hang Chan, Zaofeng Yang, Iris L. K. Wong, Larry M.C. Chow, Chin Fung Chan, Xianliang Zhao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
chemistry.chemical_classification 0303 health sciences biology 030306 microbiology Flavonoid medicine.disease Leishmania biology.organism_classification In vitro Lesion 03 medical and health sciences Infectious Diseases chemistry Cutaneous leishmaniasis medicine Pharmacology (medical) Experimental Therapeutics medicine.symptom Amastigote IC50 Incubation 030304 developmental biology |
| Zdroj: | Antimicrob Agents Chemother |
| Popis: | 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 (IC(50)) of 0.3 μM 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%). |
| Databáze: | OpenAIRE |
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