Antibacterial efficacy evaluation and mechanism probe of small lysine chalcone peptide mimics
Copyright © 2022 Elsevier Masson SAS. All rights reserved..
Bacterial resistance is a growing threat to public health and a significant barrier to anti-infective treatment. Consequently, the development of novel antibacterial strategies to address this issue is critical. Herein, we developed a series of chalcone-alkyl-lysine compounds by mimicking the chemical structure and antibacterial properties of cationic antimicrobial peptides. Most of the compounds showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. Compound 6d displayed potent antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), with MICs of 1-4 μg/mL. In addition, 6d exhibited excellent antibacterial activity against clinical MRSA and NDM-positive isolates, bactericidal properties, low resistance frequency. The mechanism studies revealed that compound 6d destroys bacterial cell membranes by interacting with phosphatidylglycerol (PG), causing the production of reactive oxygen species (ROS) and the leakage of nucleic acids, resulting in bacterial death. Furthermore, compound 6d did not exhibit any observable toxicity in HeLa and HEK293 cells at 8 × MIC. As a result, the findings suggest that compound 6d has potential therapeutic effects against bacterial infections and could be a promising drug candidate for future research.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:244 |
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| Enthalten in: |
European journal of medicinal chemistry - 244(2022) vom: 15. Dez., Seite 114885 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shen, Bo-Yuan [VerfasserIn] |
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| Links: |
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| Themen: |
5S5A2Q39HX |
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| Anmerkungen: |
Date Completed 21.11.2022 Date Revised 21.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2022.114885 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348483228 |
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| 520 | |a Copyright © 2022 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Bacterial resistance is a growing threat to public health and a significant barrier to anti-infective treatment. Consequently, the development of novel antibacterial strategies to address this issue is critical. Herein, we developed a series of chalcone-alkyl-lysine compounds by mimicking the chemical structure and antibacterial properties of cationic antimicrobial peptides. Most of the compounds showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. Compound 6d displayed potent antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), with MICs of 1-4 μg/mL. In addition, 6d exhibited excellent antibacterial activity against clinical MRSA and NDM-positive isolates, bactericidal properties, low resistance frequency. The mechanism studies revealed that compound 6d destroys bacterial cell membranes by interacting with phosphatidylglycerol (PG), causing the production of reactive oxygen species (ROS) and the leakage of nucleic acids, resulting in bacterial death. Furthermore, compound 6d did not exhibit any observable toxicity in HeLa and HEK293 cells at 8 × MIC. As a result, the findings suggest that compound 6d has potential therapeutic effects against bacterial infections and could be a promising drug candidate for future research | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antibacterial activity | |
| 650 | 4 | |a Antimicrobial peptides mimics | |
| 650 | 4 | |a Chalcone | |
| 650 | 4 | |a Drug-resistant | |
| 650 | 4 | |a Membrane | |
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| 700 | 1 | |a Wang, Ming-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shuai-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Sen |e verfasserin |4 aut | |
| 700 | 1 | |a Ampomah-Wireko, Maxwell |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Sheng-Cong |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Da-Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Shangshang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, En |e verfasserin |4 aut | |
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