Synthesis and in vitro biological evaluation of 2-(phenylcarbamoyl)phenyl 4-substituted benzoates

Martin Krátký, Szilvia Bosze, Zsuzsa Baranyai, Ildikó Szabó, Jiřina Stolaříková, Georgios Paraskevopoulos, Jarmila Vinšová

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13 Citations (Scopus)

Abstract

Based on the previously described antimicrobial activity of salicylanilide derivatives, we designed and synthesized novel 2-(phenylcarbamoyl)phenyl 4-substituted benzoates. The most active salicylanilides were selected for esterification by various 4-substituted benzoic acids. These compounds were evaluated in vitro against Mycobacterium tuberculosis, including multidrug-resistant strains, nontuberculous mycobacteria (Mycobacterium avium and Mycobacterium kansasii), and eight bacterial and fungal strains. We also investigated the cytostatic and cytotoxic actions of the esters. The minimum inhibitory concentrations (MICs) against mycobacteria ranged from 0.125 to 8 μM. Interestingly, the drug-resistant strains exhibited the highest susceptibility without any cross-resistance with established drugs. 4-Bromo-2-[4-(trifluoromethyl)phenylcarbamoyl]phenyl 4-nitrobenzoate showed the most potent inhibition with MIC values ranging from 0.25 to 2 μM. Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, were inhibited by two derivatives with MIC values of at least 0.49 μM, whereas Gram-negative bacteria and most of the tested fungi did not display any marked susceptibility. Benzoates exhibited no cytotoxicity at concentrations up to 50 μM but most caused significant cytostasis with IC50 values lower than 10 μM. Some cytotoxicity-based selectivity indexes for drug-susceptible and drug-resistant M. tuberculosis as well as Staphylococci were higher than 100. These values indicate that some of these derivatives are promising candidates for future research.

Original languageEnglish
Pages (from-to)868-875
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number4
DOIs
Publication statusPublished - Feb 15 2015

Keywords

  • Antimicrobial activity
  • Benzoate
  • Cytostasis
  • Cytotoxicity
  • Ester
  • In vitro activity
  • Multidrug-resistant tuberculosis
  • Mycobacterium tuberculosis
  • Nontuberculous mycobacteria
  • Salicylanilide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Krátký, M., Bosze, S., Baranyai, Z., Szabó, I., Stolaříková, J., Paraskevopoulos, G., & Vinšová, J. (2015). Synthesis and in vitro biological evaluation of 2-(phenylcarbamoyl)phenyl 4-substituted benzoates. Bioorganic and Medicinal Chemistry, 23(4), 868-875. https://doi.org/10.1016/j.bmc.2014.12.019