Wu, Xi-Ying and Zhao, Ze-Yu and Osman, Ezzat E.A. and Wang, Xiao-Juan and Choo, Yeun Mun and Benjamin, Menny M. and Xiong, Juan and Hamann, Mark T. and Luo, Cheng and Hu, Jin-Feng (2024) Platanosides from Platanus × acerifolia: New molecules, SAR, and target validation of a strong lead for drug-resistant bacterial infections and the associated sepsis. Bioorganic Chemistry, 143. ISSN 0045-2068, DOI https://doi.org/10.1016/j.bioorg.2024.107103.
Full text not available from this repository.Abstract
Three undescribed (1–3) and nine known (4–12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 μg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 μg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 μM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead. © 2024 Elsevier Inc.
| Item Type: | Article |
|---|---|
| Funders: | National Center for Complementary and Integrative Health [Grant no. RO1AT0072318-01], National Natural Science Foundation of China [Grant no. 21937002, 81773599, 82003659] |
| Uncontrolled Keywords: | Antibacterial; Enterococcus faecium; Molecular docking; Molecular ion networking (MoIN); Platanosides; Platanus × acerifolia; Staphylococcus aureus; Structure-activity relationship (SAR); Target validation |
| Subjects: | Q Science > QD Chemistry R Medicine |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 03 Jul 2024 06:45 |
| Last Modified: | 03 Jul 2024 06:45 |
| URI: | http://eprints.um.edu.my/id/eprint/44821 |
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