Action mechanism of 6, 6'-dihydroxythiobinupharidine from Nuphar japonicum, which showed anti-MRSA and anti-VRE activities

Biochimica Et Biophysica Acta
Shinya OkamuraTeruo Kuroda

Abstract

Multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), cause serious infections at clinical sites, for which the development of new drugs is necessary. We screened candidates for new antibiotics and investigated its action mechanism. An antimicrobial compound was isolated from an extract of Nuphar japonicum. Its chemical structure was determined by NMR, MS, and optical rotation. We measured its minimum inhibitory concentration (MIC) using the microdilution method. The effects of the compound on DNA gyrase and DNA topoisomerase IV were investigated with DNA supercoiling, decatenation, and cleavage assay. We isolated and identified 6,6'-dihydroxythiobinupharidine as the antimicrobial compound. The MIC of this compound was 1-4 μg/mL against various MRSA and VRE strains. We also demonstrated that this compound inhibited DNA topoisomerase IV (IC50 was 10-15 μM), but not DNA gyrase in S. aureus, both of which are known to be the targets of quinolone antibiotics and necessary for DNA replication. However, this compound only exhibited slight cross-resistance to norfloxacin-resistant S. aureus, which indicated that DTBN might inhibit other targets besides topo...Continue Reading

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Citations

Jul 15, 2016·ACS Central Science·Norihiro TadaRyan A Shenvi
Mar 16, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuuki ShimozuTsutomu Hatano
Feb 28, 2020·Natural Product Reports·Lie-Feng MaZha-Jun Zhan
Apr 9, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hila WinerJacob Gopas
Apr 7, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Teruo Kuroda, Wakano Ogawa
Jul 2, 2019·Chemical & Pharmaceutical Bulletin·Hisashi MatsudaMasayuki Yoshikawa
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kamran WaidhaJacob Gopas
Jul 9, 2021·European Journal of Medicinal Chemistry·Lima RodriguesMahesh S Majik
Sep 16, 2017·Journal of the American Chemical Society·Jacob J LacharityArmen Zakarian
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kamran WaidhaAvi Golan-Goldhirsh

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