Biological evaluation of bisbenzaldehydes against four Mycobacterium species

Davie Cappoen; Delphine Forge; Frank Vercammen; Vanessa Mathys; Mehdi Kiass; Virginie Roupie; Roel Anthonissen; Luc Verschaeve; Jean Jacques Vanden Eynde; Kris Huygen

doi:10.1016/j.ejmech.2013.03.023

Biological evaluation of bisbenzaldehydes against four Mycobacterium species

Eur J Med Chem. 2013 May:63:731-8. doi: 10.1016/j.ejmech.2013.03.023. Epub 2013 Mar 18.

Authors

Davie Cappoen¹, Delphine Forge, Frank Vercammen, Vanessa Mathys, Mehdi Kiass, Virginie Roupie, Roel Anthonissen, Luc Verschaeve, Jean Jacques Vanden Eynde, Kris Huygen

Affiliation

¹ Program Host-Pathogen Interactions, Service Immunology, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health WIV-ISP (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium.

PMID: 23567963
DOI: 10.1016/j.ejmech.2013.03.023

Abstract

A series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant Mycobacterium tuberculosis, against virulent Mycobacterium bovis, against Mycobacterium ulcerans and against two Mycobacterium avium subspecies. Among the 33 substances that were tested, compound 12, i.e. 4,4'-[1,12-dodecanediyl(oxy)]bisbenzaldehyde, emerged as the most promising hit. Its activity was further confirmed in an intracellular growth inhibition assay of M. tb in murine J774 A.1 macrophages. None of the compounds showed significant cytotoxicity on human C3A hepatocytes in a neutral red dye uptake assay and no genotoxicity or mutagenicity was observed as demonstrated by a VITOTOX™ test and confirmed with a comet assay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Benzaldehydes / chemistry
Benzaldehydes / pharmacology*
Cell Line
Cell Survival / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Drug Resistance, Bacterial / drug effects
Hepatocytes / cytology
Hepatocytes / drug effects
Host-Pathogen Interactions / drug effects
Humans
Macrophages / cytology
Macrophages / drug effects
Macrophages / microbiology
Mice
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium / classification
Mycobacterium / drug effects*
Mycobacterium / physiology
Mycobacterium avium / drug effects
Mycobacterium avium / physiology
Mycobacterium bovis / drug effects
Mycobacterium bovis / physiology
Mycobacterium tuberculosis / drug effects
Mycobacterium tuberculosis / physiology
Mycobacterium ulcerans / drug effects
Mycobacterium ulcerans / physiology
Species Specificity

Substances

4,4'-(1,12-dodecanediyl(oxy))bisbenzaldehyde
Anti-Bacterial Agents
Antitubercular Agents
Benzaldehydes