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1. Introduction

The worldwide epidemic of antibiotic resistance is in danger of ending the “golden age” of antibiotic therapy and therefore is touching all people [1]. Major current problems arise from the spread of nosocomial antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β -lactamases-producing (ESBL) Escherichia coli or Klebsiella spp., multiresistant Pseudomonas, or Acinetobacter sp. as well as Clostridium difficile [2].

The situation in the fungal kingdom is a bit different. Over the past decades there has been a growing number of immunocompromised patients (e.g., patients with AIDS or after transplantations) who can develop opportunistic mycoses caused by expanding spectrum of fungal pathogens, including those with problematic susceptibility to current antifungal drugs. Pathogenic fungi can use different mechanisms of resistance to diverse drugs with unrelated modes of action [3].

The searching for potential antimicrobial agents is still challenging and new groups of compounds are desired [4].

Various salicylanilide (2-hydroxy-N-phenylbenzamide) esters have displayed good antibacterial and antifungal activities, especially against Gram-positive strains [5–7]. Recently salicylanilides were described besides an excellent antibacterial acting against both drug-sensitive and methicillin-resistant S. aureus inhibition activity towards bacterial transglycosylase, an enzyme necessary for the formation of the cell wall [8].

Benzoic acid alone is known as a nonspecific antimicrobial agent with the wide spectrum of the activities against human pathogenic fungi and bacteria with different minimum inhibitory concentration (MIC) values [9–14]; moreover it was being evaluated as an inhibitor of β -carbonic anhydrase, a new molecular target occurring in C. albicans and Cryptococcus neoformans [15]. The review of the benzoic acid as preservative agent, the mechanisms of action, and resistance were published [16].

Based on these facts, we designed and evaluated new salicylanilide benzoates as potential antibacterial and antifungal agents.

2. Material and Methods

2.1. Chemistry

Salicylanilides were prepared by the procedure described previously [7]. The esters were prepared from salicylanilides by using benzoic acid and N,N′-dicyclohexylcarbodiimide as dehydrating and condensation agent (e.g., [7]). The general structure is presented in the head of Table 1.

Table 1

Antibacterial activity of benzoates 1-18.
MIC/IC80 [μmol/L]
R1 R2 Staphylococcus aureus MRSA S. aureus Staphylococcus epidermidis Enterococcus sp. Pseudomonas aeruginosa
24 h 48 h 24 h 48 h 24 h 48 h 24 h 48 h 24 h 48 h

  

  

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