Antifungal Activity of Salicylanilides and Their Esters with 4-(Trifluoromethyl)benzoic Acid

Abstract

Searching for novel antimicrobial agents still represents a current topic in medicinal chemistry. In this study, the synthesis and analytical data of eighteen salicylanilide esters with 4-(trifluoromethyl)benzoic acid are presented. They were assayed in vitro as potential antimycotic agents against eight fungal strains, along with their parent salicylanilides. The antifungal activity of the presented derivatives was not uniform and moulds showed a higher susceptibility with minimum inhibitory concentrations (MIC) ≥ 0.49 µmol/L than yeasts (MIC ≥ 1.95 µmol/L). However, it was not possible to evaluate a range of 4-(trifluoromethyl)benzoates due to their low solubility. In general, the most active salicylanilide was N-(4-bromophenyl)-4-chloro-2-hydroxybenzamide and among esters, the corresponding 2-(4-bromophenylcarbamoyl)-5-chlorophenyl 4-(trifluoromethyl) benzoate exhibited the lowest MIC of 0.49 µmol/L. However, the esterification of salicylanilides by 4-(trifluoromethyl)benzoic acid did not result unequivocally in a higher antifungal potency.

Antibacterial Activity of Salicylanilide 4-(Trifluoromethyl)-benzoates

“…For the remaining ten esters ( 1a , 1c , 1d , 1f , 1g , 1i , 1l , 1n , 1q , 1r ), whose MICs are not reported, it was not possible to determine them. Similarly as in previously reported antifungal assay [ 22 ], they could not be dissolved in the testing medium well or they precipitated rapidly in them due to an escalated lipophilicity. 4-(Trifluoromethyl)benzoic acid showed no antibacterial action under our conditions (MIC > 500 µmol/L).…”

“…The synthesis and characterization of the salicylanilide 4-(trifluoromethyl)benzoates ( Scheme 1 ) were published recently [ 22 ]. Yield of esters synthesized via N , N '-dicyclohexylcarbodiimide coupling ranged from 49% up to 86%.…”

“…Salicylanilide benzoates revealed a notable activity especially toward MDR-TB [ 13 ] as well as antibacterial one [ 11 ]. Aromatic esters of 4-(trifluoromethyl)benzoic acid have been reported as a mild antibacterial agents against Pseudomonas fluorescens and Bacillus subtilis , since inactive for S. aureus and E. coli [ 21 ], and some salicylanilide 4-(trifluoromethyl)benzoates exhibited antifungal activity, especially against moulds with MICs ≥ 0.49 μmol/L [ 22 ]. Additionally, an increased lipophilicity may ameliorate passing through cell walls and biomembranes, that is why we selected highly lipophilic salicylanilide 4-(trifluoromethyl)benzoates for the searching of a potential antibacterial and antimycobacterial agents with expected lower MIC.…”

Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity

“…The sulfadiazine derivatives 1 – 2 were screened in vitro for their antimicrobial properties. The panel of pathogens involved Staphylococcus aureus CCM 4516/08, methicillin-resistant Staphylococcus aureus H 5996/08 (MRSA), Staphylococcus epidermidis H 6966/08, Enterococcus faecalis J 14365/08 (Gram-positive bacteria), Escherichia coli CCM 4517, Klebsiella pneumoniae D 11750/08, extended spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae J 14368/08, and Pseudomonas aeruginosa CCM 1961 (Gram-negative strains) ( Table 1 ), mycobacteria Mycobacterium tuberculosis 331/88 (H 37 Rv), Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and the clinical isolate 6509/96 ( Table 2 ) [ 16 ], and fungal species of Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445 ( Table 3 ) [ 17 ]. This panel of twenty microbial species covers a wide range of important human pathogens including those with an acquired resistance.…”

“…The MIC values were determined after 24 and 48 h of incubation in the dark at 35 °C (±0.1) in a humid atmosphere. For T. interdigitale , the final MIC values were determined after 72 and 120 h of incubation [ 17 ].…”