Pharmacologically active salicylanilides (2-hydroxy-N-phenylbenzamides) have been a promising area of interest in medicinal chemistry-related research for quite some time. This group of compounds has shown a wide spectrum of biological activities, including but not limited to anticancer effects. In this study, substituted salicylanilides were chosen to evaluate the in vitro activity on U87 human glioblastoma (GBM) cells. The parent salicylanilide, salicylanilide 5-chloropyrazinoates, a 4-aminosalicylic acid derivative, and the new salicylanilide 4-formylbenzoates were chemically and in vitro characterized. To enhance the internalization of the compounds, they were conjugated to delivery peptides with the formation of oxime bonds. Oligotuftsins ([TKPKG]n, n = 1-4), the ligands of neuropilin receptors, were used as GBM-targeting carrier peptides. The in vitro cellular uptake, intracellular localization, and penetration ability on tissue-mimicking models of the fluorescent peptide derivatives were determined. The compounds and their peptide conjugates significantly decreased the viability of U87 glioma cells. Salicylanilide compound-induced GBM cell death was associated with activation of autophagy, as characterized by immunodetection of autophagy-related processing of light chain 3 protein.

• Publication type
• Journal Article MeSH

A new series of 27 diethyl 2-(phenylcarbamoyl)phenyl phosphorothioates (thiophosphates) was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenyl)carbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 µM). The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}-phenyl) O,O-diethyl phosphorothioate with MIC values from 16 µM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition) and comparable (for BChE inhibition) activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 µM range.

• MeSH
• Acetylcholinesterase metabolism   MeSH
• Antitubercular Agents chemical synthesis   chemistry   pharmacology   MeSH
• Cholinesterase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acetylcholinesterase MeSH
• Antitubercular Agents MeSH
• Cholinesterase Inhibitors MeSH

The development of novel antimicrobial agents represents a timely research topic. Eighteen salicylanilide 4-(trifluoromethyl)benzoates were evaluated against Mycobacterium tuberculosis, M. avium and M. kansasii, eight bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and for the inhibition of mycobacterial isocitrate lyase. Some compounds were further screened against drug-resistant M. tuberculosis and for their cytotoxicity. Minimum inhibitory concentrations (MICs) for all mycobacterial strains were within 0.5-32 μmol/L, with 4-chloro-2-[4-(trifluoromethyl)phenylcarbamoyl]phenyl 4-(trifluoromethyl)benzoate superiority. Gram-positive bacteria including MRSA were inhibited with MICs ³ 0.49 μmol/L, while Gram-negative ones were much less susceptible. Salicylanilide 4-(trifluoromethyl)benzoates showed significant antibacterial properties, for many strains being comparable to standard drugs (isoniazid, benzylpenicillin) with no cross-resistance. All esters showed mild inhibition of mycobacterial isocitrate lyase and four compounds were comparable to 3-nitropropionic acid without a direct correlation between in vitro MICs and enzyme inhibition.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Benzoates pharmacology   MeSH
• Nitro Compounds pharmacology   MeSH
• Isocitrate Lyase antagonists & inhibitors   metabolism   MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Propionates pharmacology   MeSH
• Salicylanilides pharmacology   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3-nitropropionic acid MeSH Browser
• Anti-Bacterial Agents MeSH
• Benzoates MeSH
• Nitro Compounds MeSH
• Isocitrate Lyase MeSH
• Propionates MeSH
• salicylanilide MeSH Browser
• Salicylanilides MeSH

The increasing emergence especially of drug-resistant tuberculosis has led to a strong demand for new anti-tuberculosis drugs. Eighteen salicylanilide benzoates were evaluated for their inhibition potential against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii; minimum inhibitory concentration values ranged from 0.5 to 16 μmol/L. The most active esters underwent additional biological assays. Four benzoates inhibited effectively the growth of five multidrug-resistant strains and one extensively drug-resistant strain of M. tuberculosis at low concentrations (0.25–2 μmol/L) regardless of the resistance patterns. The highest rate of multidrug-resistant mycobacteria inhibition expressed 4-chloro-2-[4-(trifluoromethyl)-phenylcarbamoyl]phenyl benzoate (0.25–1 μmol/L). Unfortunately, the most potent esters were still considerably cytotoxic, although mostly less than their parent salicylanilides.

• MeSH
• Antitubercular Agents pharmacology   toxicity   MeSH
• Benzoates pharmacology   toxicity   MeSH
• Hep G2 Cells MeSH
• Inhibitory Concentration 50 MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Drug Resistance, Multiple, Bacterial MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Salicylanilides pharmacology   toxicity   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Benzoates MeSH
• Salicylanilides MeSH

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.

• MeSH
• Absidia drug effects   MeSH
• Antifungal Agents chemical synthesis   pharmacology   MeSH
• Aspergillus fumigatus drug effects   MeSH
• Benzoates chemical synthesis   pharmacology   MeSH
• Candida drug effects   MeSH
• Esterification MeSH
• Esters MeSH
• Microbial Sensitivity Tests MeSH
• Salicylanilides chemical synthesis   pharmacology   MeSH
• Toluene analogs & derivatives   chemistry   MeSH
• Trichophyton drug effects   MeSH
• Trichosporon drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 4-(trifluoromethyl)benzoic acid MeSH Browser
• Antifungal Agents MeSH
• Benzoates MeSH
• Esters MeSH
• Salicylanilides MeSH
• Toluene MeSH

The resistance to antimicrobial agents brings a need of novel antimicrobial agents. We have synthesized and found the in vitro antibacterial activity of salicylanilide esters with benzoic acid (2-(phenylcarbamoyl)phenyl benzoates) in micromolar range. They were evaluated in vitro for the activity against eight fungal and eight bacterial species. All derivatives showed a significant antibacterial activity against Gram-positive strains with minimum inhibitory concentrations ≥ 0.98 μmol/L including methicillin-resistant Staphylococcus aureus strain. The most active compounds were 5-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl benzoate and 4-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl benzoate. The antifungal activity is significantly lower.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Antifungal Agents pharmacology   MeSH
• Benzoates pharmacology   MeSH
• Magnetic Resonance Spectroscopy MeSH
• Microbial Sensitivity Tests MeSH
• Salicylanilides pharmacology   MeSH
• Spectrophotometry, Infrared MeSH
• In Vitro Techniques MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antifungal Agents MeSH
• Benzoates MeSH
• salicylanilide MeSH Browser
• Salicylanilides MeSH

A series of eighteen novel esters of salicylanilides with benzenesulfonic acid were designed, synthesized and characterized by IR, ¹H-NMR and ¹³C-NMR. They were evaluated in vitro as potential antimycobacterial agents towards Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. In general, the minimum inhibitory concentrations range from 1 to 500 µmol/L. The most active compound against M. tuberculosis was 4-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)-phenyl benzenesulfonate, with MIC of 1 µmol/L and towards M. kansasii its isomer 5-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl benzenesulfonate (MIC of 2-4 µmol/L). M. avium was the less susceptible strain. However, generally, salicylanilide benzenesulfonates did not surpass the activity of other salicylanilide esters with carboxylic acids.

• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Benzenesulfonates chemical synthesis   chemistry   pharmacology   MeSH
• Esterification MeSH
• Esters chemical synthesis   chemistry   pharmacology   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium drug effects   MeSH
• Drug Design MeSH
• Salicylanilides chemical synthesis   chemistry   pharmacology   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Benzenesulfonates MeSH
• Esters MeSH
• Salicylanilides MeSH