Synthesis and antibacterial activities of novel 4-hydroxy-7-hydroxy- and 3-carboxycoumarin derivatives

Molecules. 2012 Sep 10;17(9):10846-63. doi: 10.3390/molecules170910846.

Abstract

Coumarin derivatives are used as fluorescent dyes and medicines. They also have some notable physiological effects, including the acute hepatoxicity and carcinogenicity of certain aflatoxins, the anticoagulant action of dicoumarol, and the antibiotic activity of novobicin and coumerymycin A1. Because the number of drug resistant strains is increasing at present, the synthesis of new antibacterial compounds is one of the critical methods for treating infectious diseases. Therefore, a series of coumarinsubstituted derivatives, namely 4-hydroxy- and 7-hydroxycoumarins, and 3-carboxycoumarins were synthesized. 4-Hydroxycoumarin derivatives 4a-c underwent rearrangement reactions. Both 4- and 7-hydroxycoumarins were treated with activated aziridines which produced series of ring-opened products 7, 8, 10, and 11. 3-Carboxy-coumarin amide dimer derivatives 14-21 were prepared by reacting aliphatic alkylamines and alkyldiamines with PyBOP and DIEA. In this study, we use a new technique called modified micro-plate antibiotic susceptibility test method (MMAST), which is more convenient, more efficient, and more accurate than previous methods and only a small amount of the sample is required for the test. Some of the compounds were produced by reactions with acid anhydrides and demonstrated the ability to inhibit Gram-positive microorganisms. The dimer derivatives displayed lower antibacterial activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Hydroxycoumarins* / chemistry
  • 4-Hydroxycoumarins* / pharmacology
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Bacteria / drug effects*
  • Coumarins / chemical synthesis*
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Escherichia coli / drug effects
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Umbelliferones* / chemistry
  • Umbelliferones* / pharmacology

Substances

  • 4-Hydroxycoumarins
  • Anti-Bacterial Agents
  • Coumarins
  • Umbelliferones
  • 7-hydroxycoumarin
  • coumarin
  • 4-hydroxycoumarin