Synthesis and antimicrobial activity of β-carboline derivatives with N2-alkyl modifications

Kenji Suzuki; Itsuki Nomura; Masayuki Ninomiya; Kaori Tanaka; Mamoru Koketsu

doi:10.1016/j.bmcl.2018.06.050

Synthesis and antimicrobial activity of β-carboline derivatives with N²-alkyl modifications

Bioorg Med Chem Lett. 2018 Sep 15;28(17):2976-2978. doi: 10.1016/j.bmcl.2018.06.050. Epub 2018 Jul 6.

Authors

Kenji Suzuki¹, Itsuki Nomura², Masayuki Ninomiya³, Kaori Tanaka⁴, Mamoru Koketsu⁵

Affiliations

¹ Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
² Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
³ Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
⁴ Division of Anaerobe Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan; United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
⁵ Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: koketsu@gifu-u.ac.jp.

PMID: 30001916
DOI: 10.1016/j.bmcl.2018.06.050

Abstract

β-Carbolines constitute a vast group of indole alkaloids and exhibit various biological actions. The objective of this study was to investigate the structure-activity relationships of β-carboline derivatives on in vitro inhibitory effects against clinically relevant microorganisms. A series of β-carboline dimers and their N²-alkylated analogues were therefore prepared and evaluated for their antimicrobial effects. Among these, a dimeric 6-chlorocarboline N²-benzylated salt exerted potent activity against Staphylococcus aureus at MICs of 0.01-0.05 μmol/mL. Our work highlights that N¹-N¹ dimerization and N²-benzylation significantly enhanced the antimicrobial effects of compounds.

Keywords: Antimicrobial effect; N(1)-N(1) dimerization; N(2)-benzylation; β-Carboline.

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Candida / drug effects*
Carbolines / chemical synthesis
Carbolines / chemistry
Carbolines / pharmacology*
Dose-Response Relationship, Drug
Gram-Negative Bacteria / drug effects*
Gram-Positive Bacteria / drug effects*
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antifungal Agents
Carbolines
norharman