Effect of Bavachinin and its derivatives on T cell differentiation.

Bavachinin, which can be isolated from the Chinese herb Fructus Psoraleae, has the potential as a potent anti-asthma drug. However, the extremely low water solubility of Bavachinin limits its application. In this study, two new derivatives of Bavachinin, i.e., compounds A and B, whose water solubility is better than that of Bavachinin, were synthesized via biotransformation. A comparative investigation was then performed on the effects of these two new derivatives, along with Bavachinin, on T cell differentiation. The results showed that they have different effects. Bavachinin and compound B inhibited green fluorescent protein (GFP) production from the T cells of IL-4-GFP-enhanced transcript (4GET) mice, whereas compound A did not. The effect was mainly attributed to the inhibition of GATA-3 protein production. Bavachinin and compound B can inhibit the production of GATA-3 mRNA, but they showed different effects on the production of T-bet mRNA. Compound B increased the production of T-bet mRNA, whereas Bavachinin did not. The results will be very useful for optimizing Bavachinin so that potent anti-allergic drugs can be developed. The structure-activity relationship of Th2 was revealed based on the difference between Bavachinin and compound B. This finding can enrich the database of preliminary drug screening from their chemical structures.

Biotransformation of bavachinin by three fungal cell cultures.

Biotransformation of bavachinin (1) was investigated using three fungal cell cultures of Aspergillus flavus ATCC 30899, Cunninghamella elegans CICC 40250 and Penicillium raistrickii ATCC 10490, respectively. Two major converted products were identified by LC/MS, (1)H NMR and (13)C NMR and X-ray diffraction. Two biocatalyst systems, A. flavus ATCC 30899 and C. elegans CICC 40250 cell cultures, showed a great capacity of hydroxylation and two hydroxyl groups were attached at C-2″ and C-3″ positions in the side chain of the bavachinin A-ring, resulting in the formation of the same compound with a name, (S)-6-((R)-2,3-dihydroxy-3-methylbutyl)-2-(4-hydroxyphenyl)-7-methoxychromen-4-one (2). On the other hand, P. raistrickii ATCC 10490 cell cultures possessed the ability to reduction at C-4 of the substrate C-ring, resulting in the production of (2S,4R)-2-(4-hydroxyphenyl)-7-methoxy-6-(3-methylbut-2-en-1-yl)chromen-4-ol (3). Furthermore, the in vitro anti-tumor activities of the above compounds were evaluated by MTT assay. Compared with the substrate (1), product 3 possessed stronger inhibition activity on the human breast cancer cell line (MCF-7) and slightly lower inhibition activities against Hep G2, HeLa, Hep-2 and A549 cells lines; while the hydroxyl product 2 possessed much lower inhibition activity on tumor cells lines, which might be related to the insertion of two hydroxyl groups. Compounds 2 and 3 were considered to be novel. It was also the first time to biotransform bavachinin (1) by these three fungi, which suggested the potential role of microbial enzymes to synthesize novel compounds from plant secondary metabolites.

11α,15α-Dihy-droxy-androst-4-ene-3,17-dione.

The title compound, C(19)H(26)O(4), was biotransformed from androstenedione. In the crystal, inter-molecular O-H⋯O hydrogen bonds link molecules into a corrugated sheet, which lies parallel to the ab plane. Ring A has a slightly distorted half-chair conformation, rings B and C adopt chair conformations, while the cyclo-pentane ring D adopts a 14α-envelope conformation.