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Updated: Jun 21, 2026

Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
[F01WB-1315 A and B, two dihydroorotate dehydrogenase inhibitors from microbial metabolites]
Qiaojuan Qi1, Xinhua Lu, Zhihui Zheng
1College of Life Science, Hebei Normal University, Shijiazhuang 050016, China. qqj@sohu.com
Objective:
Dihydroorotate Dehydrogenase (DHODH) catalyzes the rate-limiting step in pyrimidine biosynthesis, and its inhibitors have been developed as drugs for treatment of immune diseases. We studied new DHODH inhibitors from microbial metabolites.
Methods:
We established a rapid and effective high throughput screening method for screening DHODH inhibitors from microbial metabolites. The active compounds were isolated from the candidate strain by column chromatography and preparative HPLC.
Results:
We picked out F01WB-1315 strain as candidate from 4560 fungal strains. We isolated two active compounds F01WB-1315A and B, with IC50 of 0.07 microg/mL and 0.51 microg/mL, respectively. F01WB-1315B could completely inhibit the spleen lymphocytes proliferation stimulated by ConA in vitro, but F01WB-1315A only had 31.62% inhibitory activity. F01WB-1315A, B were identified to be Ascofuranone and Ascochlorin by their physicochemical properties, MS, 13C-NMR and 1H-NMR analysis.
Conclusion:
F01WB-1315A and B are two strong specific DHODH inhibitors and show moderate inhibitory activity against spleen lymphocytes proliferation.
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