The lactone form of stachybotrydial: a new inhibitor of dihydrofolate reductase from Stachybotrys sp. FN298

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Title
The lactone form of stachybotrydial: a new inhibitor of dihydrofolate reductase from Stachybotrys sp. FN298
Author(s)
Yun Ju Kwon; Mi-Jin Sohn; Hyun Ju Kim; Won Gon Kim
Bibliographic Citation
Biological & Pharmaceutical Bulletin, vol. 37, no. 8, pp. 1406-1410
Publication Year
2014
Abstract
Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 μM. It also prevented the growth of S. aureus and methicillinresistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 μg?mL-1. To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA.
Keyword
Dihydrofolate reductaseStachybotrydialStachybotrysStaphylococcus aureus
ISSN
0918-6158
Publisher
Pharmaceutical Soc Japan
DOI
http://dx.doi.org/10.1248/bpb.b14-00108
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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