Discovery of cytochrome bc1 complex inhibitors inspired by the natural product karrikinolide

The cytochrome bc1 complex (cyt bc1 or complex III) is a promising target of numerous antibiotics and fungicides. With an aim to indentify new lead structures for the bc1 complex, a series of novel inhibitors were discovered from the natural product karrikinolide for the first time. Extensive screen...

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Bibliographic Details
Published in:RSC advances 2016-10, Vol.6 (100), p.97580-97586
Main Authors: Chen, Cheng, Wu, Qiong-You, Shan, Lian-Ying, Zhang, Bei, Verpoort, Francis, Yang, Guang-Fu
Format: Article
Language:English
Subjects:
Antibiotics
Cytochromes
Fungicides
Inhibitors
Natural products
Phenyls
Scaffolds
Screening
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Summary:The cytochrome bc1 complex (cyt bc1 or complex III) is a promising target of numerous antibiotics and fungicides. With an aim to indentify new lead structures for the bc1 complex, a series of novel inhibitors were discovered from the natural product karrikinolide for the first time. Extensive screening results suggested variable inhibitory activities of these compounds against succinate-cytochrome reductase [SCR, a mixture of respiratory complex II (SQR) and complex III (the bc1 complex)], implying the essential role of a 4-substituted phenyl group for the high potency. Exceptionally, compound 12g showed excellent inhibition potency having an IC50 value in the sub-micromolar range, demonstrating its higher potency than the commercial control amisulbrom by over two orders of magnitude. Further experiments inferred that these newly prepared compounds mainly target the bc1 complex. Seemingly, this work has presented a new lead scaffold for further development of bc1 complex inhibitors.
ISSN:2046-2069
DOI:10.1039/c6ra19424a