Abstract
Ursolic acid
(1)
and kaempferol
(3)
are two main cytotoxic constituents of the Mediterranean plant
Nerium oleander
[1,2]. Microbial metabolism of ursolic acid with
Aspergillus flavus
ATCC 9170 resulted in the more cytotoxic 3-oxo-derivative designated as ursonic acid
(2).
On the other hand,
Cunninghamella blakesleeana A
TCC 8688A was able to convert kaempferol into kaempferol 3-
O-β-
D-glucopyranoside
(4)
and the new natural product kaempferol 4ʹ-sulfate
(5)
. Incubation of kaempferol with
Mucor ramannianus
ATCC9628 led to the isolation of one metabolite identified as kaempferol 4ʹ-
O-α-
L-rhamnopyranoside
(6).
Transformation of kaempferol to the new compound kaempferol 7-
O-β-
D-4-
O
-methylglucopyranoside
(7)
and herbacetin 8-
O
-
β-
D-glucopyranoside
(8)
was observed when fermented with
Beauveria bassiana
ATCC 13144. Cytotoxicity of the metabolites against mammalian kidney fibroblast (Vero cells) and antitumor activity against four human tumor cell lines: malignant melanoma (SK-MEL), oral epidermal carcinoma (KB), breast ductal carcinoma (BT549) and ovary carcinoma (SK-OV3) was determined. There were three types of reactions through microbial biotransformation in this report, i.e. oxidation, glycosylation, hydroxylation as well as sulfate conjugation. This study proved that microbial transformation was a useful way to increase the diversity of the natural products as well as the conversion of abundant prototypes to rare products.
Acknowledgements
: The authors are grateful to Dr. Bharthi Avula for assistance with the HR-ESI-MS, and Mr. Frank Wiggers for assistance with the NMR data.
References:
[1] Huq MM, et al. (1999), Fitoterapia 70: 5–9. [2] Burrows GE, Tyrl RJ (2001) Toxic Plants of North America; Iowa State University Press: Ames Iowa. p78–82.