Effects of Microbial Transformation on the Biological Activities of Prenylated Chalcones from Angelica keiskei

Abstract

Microbial transformation is an alternative method for structural modification. The current study aimed at application of microbial transformation for discovering new derivatives and investigating the structure-activity relationship of isobavachalcone (1), 4-hydroxyderricin (2), and xanthoangelol (3) isolated from the herb Angelica keiskei. In the initial screening process, 1-3 were incubated with microbes using a two-stage fermentation method and analyzed through TLC monitoring. The screening results showed that Rhizopus oryzae and Mucor hiemalis were able to transform 1 and 2, respectively. Additionally, M. hiemalis and Mortierella ramanniana var. angulispora were able to transform 3. Following scale-up fermentation, four new (4, 5, 7, and 10) and five known (6, 8, 9, 11, and 12) metabolites were produced. Cytotoxicity of all the compounds (1-12) was investigated using three human cancer cell lines including A375P, HT-29, and MCF-7 by MTT method. Meanwhile, the tyrosinase inhibitory activity of 1-12 was evaluated using l-tyrosine as a substrate. Overall, 1 and 3 displayed the highest cytotoxicity, and 5 and 7 exhibited the most potent tyrosinase inhibitory activity with relatively low cytotoxicity. This allowed us to postulate that the introduction of 4'-O-glucopyranosyl group led to the reduction in cytotoxicity and improvement in tyrosinase inhibitory activity.

Keywords: 4-hydroxyderricin; Angelica keiskei; cytotoxicity; isobavachalcone; microbial transformation; tyrosinase inhibition; xanthoangelol.

Scheme 1

Two-stage fermentation method for screening.

Figure 1

Compounds 4–12 obtained by microbial transformation of 1–3.

Figure 2

Key COSY (¹H-¹H) and HMBC (¹H→¹³C) correlations of compounds 7 and 10.

Figure 3

The structural similarity between 4-hydroxychalcone and tyrosine.