Affiliations 

  • 1 Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University, Zhejiang 318000, PR China; School of Pharmacy, Fudan University, Shanghai 201203, PR China; Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, PR China
  • 2 Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University, Zhejiang 318000, PR China; School of Pharmacy, Fudan University, Shanghai 201203, PR China
  • 3 Department of Medicinal Chemistry, Theodor Bilharz Research Institute, Kornaish El-Nile St., Giza 12411, Egypt
  • 4 School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, PR China; Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston 29425-5700, USA
  • 5 Chemistry Department, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. Electronic address: ymchoo@um.edu.my
  • 6 Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston 29425-5700, USA
  • 7 School of Pharmacy, Fudan University, Shanghai 201203, PR China
  • 8 Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston 29425-5700, USA. Electronic address: hamannm@musc.edu
  • 9 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, PR China
  • 10 Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University, Zhejiang 318000, PR China; School of Pharmacy, Fudan University, Shanghai 201203, PR China; Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston 29425-5700, USA. Electronic address: jfhu@fudan.edu.cn
Bioorg Chem, 2024 Feb;143:107103.
PMID: 38211549 DOI: 10.1016/j.bioorg.2024.107103

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.