Antifungal activity of compound

Document Type

Conference Proceeding

Publication Date

2010

Abstract

Background: Candidasis is one of the most commonly encountered human fungal infections and is caused by Candida species, most notably C. albicans. The opportunistic fungal pathogen exists as part of the normal microbiota, but can become invasive in immunocompromised patients with AIDs, cancers or organ transplantation. Superficial candidiasis is common but disseminated infections are usually fatal. Antifungal treatments include flucytasine, polyenes, azoles and echinocandines. Unfortunately, they may have toxic side effects, limited spectrum of activity and poor absorption. Alarmingly, extensive use of antifungal agents has resulted in the emergence of resistant Candida infections in clinical settings. There is thus an urgent need for new antifungal agents.

Methods: Using broth dilution assay, we identified a compound (#205; 5,6,7-trihydroxy-2-phenylchromen-4-one) from a natural compund library (n = 400) with potent anti-Candidal activity against a clinical strain C. albicans CA12. Compound #205, also known as baicalein, is a major component of a Chinese herbal medicine Scutellaria baicalensis. In the present study, focused libraries of compound #205 were generated via acylation and the anti-Candidal activity was evaluated by broth dilution assay was used to evaluate the effects on membrane fluidity and efflux pumps.

Results: Focused libraries (L1-L4) of compound #205 were generated. Besides C. albicans, broth dilution assay showed that both compound #205 and L1 exhibited similar antifungal activity against non-albicans Candida (NAC) species. Lower anti-Candidal activity was observed in L2-L4, in connection with the size of the carbon chain of the acyl donors. Compound #205 and L1 were fungistatic and inhibited efflux pump activity in C. albicans and NAC species.

Conclusions: The findgins of the present study not only revealed the broad antifungal spectrum of compund #205, but also indicated the hydraxyl groups might play a pivotal role in anti-Candidal potency. Our data provided new information for stucture-activity relationship and antifungal spectrum of compound #205, which might help in further structural modifications to generate compounds with improved therapeutic potency.

Source Publication

Health Research Symposium 2010: Improving Health and Recognising Excellence, Food and Health Bureau, Hong Kong

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