Salicylanilides are pharmacologically active compounds with a wide spectrum of biological effects. Halogenated salicylanilides, which have been used for decades in human and veterinary medicine as anthelmintics, have recently emerged as candidates for drug repurposing in oncology. The most prominent example of salicylanilide anthelmintic, that is intensively studied for its potential anticancer properties, is niclosamide. Nevertheless, recent studies have discovered extensive anticancer potential in a number of other salicylanilides. This potential of their anticancer action is mediated most likely by diverse mechanisms of action such as uncoupling of oxidative phosphorylation, inhibition of protein tyrosine kinase epidermal growth factor receptor, modulation of different signaling pathways as Wnt/β-catenin, mTORC1, STAT3, NF-κB and Notch signaling pathways or induction of B-Raf V600E inhibition. Here we provide a comprehensive overview of the current knowledge about the proposed mechanisms of action of anticancer activity of salicylanilides based on preclinical in vitro and in vivo studies, or structural requirements for such an activity.

• Klíčová slova
• STAT3, TK EGFR, anticancer properties, drug repurposing, mitochondrial uncoupling, niclosamide, salicylanilides,
• MeSH
• anthelmintika * farmakologie   MeSH
• lidé MeSH
• niklosamid farmakologie   MeSH
• salicylanilidy * farmakologie   chemie   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• anthelmintika * MeSH
• niklosamid MeSH
• salicylanilidy * MeSH

A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action.

• MeSH
• antitumorózní látky chemická syntéza   chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• DNA metabolismus   MeSH
• doxorubicin farmakologie   MeSH
• HCT116 buňky MeSH
• interkalátory farmakologie   MeSH
• knihovny malých molekul chemie   farmakologie   MeSH
• lidé MeSH
• molekulární modely MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• naftoly chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• racionální návrh léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-naphthol MeSH Prohlížeč
• antitumorózní látky MeSH
• calf thymus DNA MeSH Prohlížeč
• DNA MeSH
• doxorubicin MeSH
• interkalátory MeSH
• knihovny malých molekul MeSH
• nádorový supresorový protein p53 MeSH
• naftoly MeSH

A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• benzoáty chemická syntéza   farmakologie   MeSH
• karbamáty chemická syntéza   farmakologie   MeSH
• Mycobacterium avium subsp. paratuberculosis účinky léků   MeSH
• rozpřahující látky chemická syntéza   farmakologie   MeSH
• Spinacia oleracea účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• benzoáty MeSH
• karbamáty MeSH
• rozpřahující látky MeSH

In this study, a series of twenty-two ring-substituted 3-hydroxy-N-phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide showed high biological activity (MIC = 55.0 µmol/L) against S. aureus as well as methicillin-resistant strains. N-(2-Fluorophenyl)-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC = 28.4 µmol/L) against M. marinum than the standard isoniazid and 3-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide expressed higher activity (MIC = 13.0 µmol/L) against M. kansasii than the standard isoniazid. Cytotoxicity assay of effective antimicrobial compounds was performed using the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC50 value of the most active compound 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide was 16.9 μmol/L. The structure-activity relationships of all compounds are discussed.

• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• chloroplasty účinky léků   MeSH
• fotosyntéza účinky léků   MeSH
• herbicidy chemická syntéza   farmakologie   MeSH
• hydraziny chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• Spinacia oleracea účinky léků   MeSH
• Staphylococcus aureus účinky léků   MeSH
• transport elektronů účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• herbicidy MeSH
• hydraziny MeSH

A series of twenty-five novel salicylanilide N-alkylcarbamates were investigated as potential acetylcholinesterase inhibitors. The compounds were tested for their ability to inhibit acetylcholinesterase (AChE) from electric eel (Electrophorus electricus L.). Experimental lipophilicity was determined, and the structure-activity relationships are discussed. The mode of binding in the active site of AChE was investigated by molecular docking. All the discussed compounds expressed significantly higher AChE inhibitory activity than rivastigmine and slightly lower than galanthamine. Disubstitution by chlorine in C'(₃,₄) of the aniline ring and the optimal length of hexyl-undecyl alkyl chains in the carbamate moiety provided the most active AChE inhibitors. Monochlorination in C'(₄) exhibited slightly more effective AChE inhibitors than in C'(₃). Generally it can be stated that compounds with higher lipophilicity showed higher inhibition, and the activity of the compounds is strongly dependent on the length of the N-alkyl chain.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• Electrophorus metabolismus   MeSH
• fenylkarbamáty metabolismus   MeSH
• galantamin metabolismus   MeSH
• karbamáty chemie   farmakologie   MeSH
• katalytická doména MeSH
• molekulární modely MeSH
• rivastigmin MeSH
• salicylanilidy chemie   farmakologie   MeSH
• simulace molekulového dockingu MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• fenylkarbamáty MeSH
• galantamin MeSH
• karbamáty MeSH
• rivastigmin MeSH
• salicylanilide MeSH Prohlížeč
• salicylanilidy 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 účinky léků   MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• Aspergillus fumigatus účinky léků   MeSH
• benzoáty chemická syntéza   farmakologie   MeSH
• Candida účinky léků   MeSH
• esterifikace MeSH
• estery MeSH
• mikrobiální testy citlivosti MeSH
• salicylanilidy chemická syntéza   farmakologie   MeSH
• toluen analogy a deriváty   chemie   MeSH
• Trichophyton účinky léků   MeSH
• Trichosporon účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-(trifluoromethyl)benzoic acid MeSH Prohlížeč
• antifungální látky MeSH
• benzoáty MeSH
• estery MeSH
• salicylanilidy MeSH
• toluen 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
• antibakteriální látky farmakologie   MeSH
• antifungální látky farmakologie   MeSH
• benzoáty farmakologie   MeSH
• magnetická rezonanční spektroskopie MeSH
• mikrobiální testy citlivosti MeSH
• salicylanilidy farmakologie   MeSH
• spektrofotometrie infračervená MeSH
• techniky in vitro MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• benzoáty MeSH
• salicylanilide MeSH Prohlížeč
• salicylanilidy MeSH

In this study, a series of twenty-two 5-chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benzamides and ten 4-chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benzamides is described. The compounds were analyzed using RP-HPLC to determine lipophilicity. Primary in vitro screening of the synthesized compounds was performed against mycobacterial, bacterial and fungal strains. They were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The compounds showed biological activity comparable with or higher than the standards isoniazid, fluconazole, penicillin G or ciprofloxacin. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• benzamidy chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium účinky léků   MeSH
• transport elektronů MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• benzamidy MeSH

In this study, a series of twelve ring-substituted salicylanilides and carbamoylphenylcarbamates were prepared and characterized. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Moreover, their site of action in the photosynthetic apparatus was determined. Primary in vitro screening of the synthesized compounds was also performed against mycobacterial, bacterial and fungal strains. Several compounds showed biological activity comparable with or higher than the standards 3-(3,4-dichlorophenyl)-1,1-dimethylurea, isoniazid, penicillin G, ciprofloxacin or fluconazole. The most active compounds showed minimal anti-proliferative activity against human cells in culture, indicating they would have low cytotoxicity. For all compounds, the relationships between lipophilicity and the chemical structure are discussed.

• MeSH
• Absidia účinky léků   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• fenylkarbamáty chemická syntéza   chemie   farmakologie   MeSH
• fotosyntéza účinky léků   MeSH
• herbicidy chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• salicylanilidy chemická syntéza   chemie   farmakologie   MeSH
• Spinacia oleracea účinky léků   metabolismus   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Staphylococcus epidermidis účinky léků   MeSH
• transport elektronů účinky léků   MeSH
• Trichophyton účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• fenylkarbamáty MeSH
• herbicidy MeSH
• salicylanilidy MeSH