Antimicrobial Constituents from Machaerium Pers. Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens

Ilias Muhammad, Melissa R. Jacob, Mohamed A. Ibrahim, Vijayasankar Raman, Mallika Kumarihamy, Mei Wang, Taha Al-Adhami, Charlotte Hind, Melanie Clifford, Bethany Martin, Jianping Zhao, J. Mark Sutton, Khondaker Miraz Rahman

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3 Citations (Scopus)

Abstract

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6–9) and machaeridiols A-C (10–12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, −1708, −1717, −33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6–8 and 10–12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32-and >8-fold reduction of MIC’s, compared to 12, against MRSA 1708 and −1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5–8 µg/mL for two strains of Acinetobacter baumannii, 2–16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.

Original languageEnglish
Article number6000
JournalMolecules (Basel, Switzerland)
Volume25
Issue number24
DOIs
Publication statusPublished - 1 Dec 2020

Bibliographical note

Funding Information:
Funding: This work was supported in part by the USDA Agricultural Research Service Specific Cooperative Agreement No. 58-6060-6-015, and the NIH, NIAID, Division of AIDS, grant no. AI 27094. Work at PHE was supported by Grant in aid funding through an Open Innovation programme (Project 111742).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • 5-epi-machaerifurogerol
  • MRSA
  • Machaerium Rimachi 12161
  • VRE
  • gram negative bacteria
  • isoflavonoid
  • machaeridiol A–C
  • machaerifurogerol
  • machaeriol A–C

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