Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-β-carboline derivatives as potential antibacterial agents.

Autor: Song YZ; Zibo Hospital of Traditional Chinese Medicine, Zibo 255000, China., Zhang J; School of Biological Science and Technology, University of Jinan, Jinan 250022, China., Song QJ; Zibo Hospital of Traditional Chinese Medicine, Zibo 255000, China., Zhu WH; Zibo Hospital of Traditional Chinese Medicine, Zibo 255000, China., Yuan C; Zoucheng Administration for Market Regulation, Zoucheng 273100, China., Wang KM; School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_wangkm@ujn.edu.cn., Jiang CS; School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_jiangcs@ujn.edu.cn.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Sep 01; Vol. 109, pp. 129822. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.bmcl.2024.129822
Abstrakt: The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-β-carboline (THβC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THβC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THβC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: