Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, <i>Corynebacterium matruchotii</i>, via Bioactivity-HiTES
- Authors
- Lee, Da Yeong; Kim, Jonghwan; Lee, Gyu Sung; Park, Sehwan; Song, Jeongwon; Lee, Bum Soo; Lee, Seoung Rak; Kim, Ki Hyun; Kim, Chung Sub
- Issue Date
- 21-Mar-2024
- Publisher
- AMER CHEMICAL SOC
- Citation
- ACS CHEMICAL BIOLOGY, v.19, no.4, pp 973 - 980
- Pages
- 8
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS CHEMICAL BIOLOGY
- Volume
- 19
- Number
- 4
- Start Page
- 973
- End Page
- 980
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/110535
- DOI
- 10.1021/acschembio.3c00798
- ISSN
- 1554-8929
1554-8937
- Abstract
- In the field of natural product research, the rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation, and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, the human oral bacterium, with 3120 clinical drugs as potential elicitors. As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with an IC50 value of 185.7 mu M. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 mu M, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 mu M through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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