Microbial Metabolites of 7, 8-dimethoxyflavone and 5-methoxyflavone

In selecting methoxyflavones as potential chemopreventive agents it is important to determine how susceptible they are towards metabolism [1]. Since, microorganisms are predictive models for mammalian drug metabolism we investigated prospectively the microbial metabolism of 7, 8-dimethoxyflavone (1) and 5-methoxyflavone (8) using 40 microorganisms. Transformation of 7, 8-dimethoxyflavone (1) by Mucor ramannianus produced five metabolites: 7, 8-dimethoxy-4ʹ-hydroxyflavone (2), 3ʹ, 4ʹ-dihydroxy-7, 8-dimethoxyflavone (3), 7, 3ʹ-dihydroxy-8-methoxyflavone (4), 7, 4ʹ-dihydroxy-8-methoxyflavone (5) and 8-methoxy-7, 3ʹ, 4ʹ-trihydroxyflavone (6) (Table 1). It was however, completely converted to a single metabolite, 7-hydroxy-8-methoxyflavone (7) by Aspergillus flavus. 5-Methoxyflavone (8) when fermented with Beauveria bassiana gave a single product, 5-methoxyflavanone (9). Conversion of 8 with Aspergillus alliaceus yielded the metabolite, 4ʹ-hydroxy-5-methoxyflavone (10). The structures were established by spectroscopic methods. Compound 1 showed moderate susceptibility towards oxidative metabolism [1]. 5-Methoxyflavone which was highly resistant to human microsomal oxidation [1] underwent transformation to metabolites 9 (7.47%) and 10 (71.92%) when fermented with B.’bassiana and A. alliaceus respectively.

Acknowledgements: This work was supported, in part, by the United States Department of Agriculture, Agricultural Research Specific Cooperative Agreement No. 58-6408-2-00009. References: [1] Walle UK, Walle T, (2007) Drug Metab. Dispos., 35: 1985–1989.

Table 1

	1	2	3	4	5	6	7	8	9	10
R1	OMe	OMe	OMe	OMe	OMe	OMe	OMe	H	H	H
R2	OMe	OMe	OMe	OH	OH	OH	OH	H	H	H
R3	H	H	H	H	H	H	H	OMe	OMe	OMe
R4	H	H	OH	OH	H	OH	H	H	H	H
R5	H	OH	OH	H	OH	OH	H	H	H	OH
									C-2,3 dihydro