A set of twenty-four 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by combinations of methoxy/methyl/fluoro/chloro/bromo and ditrifluoromethyl groups at different positions, was prepared. The compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3,5-Difluorophenyl)-, N-(3,5-dimethylphenyl)-, N-(2,5-difluorophenyl)- and N-(2,5-dimethylphenyl)-3-hydroxynaphthalene-2-carboxamides showed the highest PET-inhibiting activity (IC50 ~ 10 µM) within the series. These compounds were able to inhibit PET in photosystem II. It has been found that PET-inhibiting activity strongly depends on the position of the individual substituents on the anilide ring and on the lipophilicity of the compounds. The electron-withdrawing properties of the substituents contribute towards the PET activity of these compounds.

• Klíčová slova
• PET inhibition, hydroxynaphthalene-carboxamides, spinach chloroplasts, structure-activity relationships,
• MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• fotosyntéza účinky léků   MeSH
• fotosystém II (proteinový komplex) antagonisté a inhibitory   metabolismus   MeSH
• herbicidy chemie   metabolismus   MeSH
• naftaleny chemie   metabolismus   MeSH
• Spinacia oleracea účinky léků   metabolismus   MeSH
• transport elektronů účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fotosystém II (proteinový komplex) MeSH
• herbicidy MeSH
• naftaleny MeSH

A series of twenty-two novel N-(disubstituted-phenyl)-3-hydroxynaphthalene- 2-carboxamide derivatives was synthesized and characterized as potential antimicrobial agents. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[2-chloro-5-(trifluoromethyl)phenyl]-3-hydroxy- naphthalene-2-carboxamide showed submicromolar (MICs 0.16-0.68 µM) activity against methicillin-resistant Staphylococcus aureus isolates. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[4-bromo-3-(trifluoromethyl)phenyl]-3-hydroxynaphthalene-2-carboxamide revealed activity against M. tuberculosis (both MICs 10 µM) comparable with that of rifampicin. Synergistic activity was observed for the combinations of ciprofloxacin with N-[4-bromo-3-(trifluoromethyl)phenyl]- and N-(4-bromo-3-fluorophenyl)-3-hydroxynaphthalene-2-carboxamides against MRSA SA 630 isolate. The similarity-related property space assessment for the congeneric series of structurally related carboxamide derivatives was performed using the principal component analysis. Interestingly, different distribution of mono-halogenated carboxamide derivatives with the -CF3 substituent is accompanied by the increased activity profile. A symmetric matrix of Tanimoto coefficients indicated the structural dissimilarities of dichloro- and dimetoxy-substituted isomers from the remaining ones. Moreover, the quantitative sampling of similarity-related activity landscape provided a subtle picture of favorable and disallowed structural modifications that are valid for determining activity cliffs. Finally, the advanced method of neural network quantitative SAR was engaged to illustrate the key 3D steric/electronic/lipophilic features of the ligand-site composition by the systematic probing of the functional group.

• Klíčová slova
• CoMSA, IVE-PLS, MIC, MTT assay, antistaphylococcal activity, antitubercular activity, hydroxynaphthalenecarboxamides, lipophilicity, similarity-activity landscape index,
• MeSH
• antiinfekční látky chemická syntéza   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium tuberculosis * MeSH
• naftaleny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiinfekční látky MeSH
• naftaleny MeSH
• naphthalene-2-carboxamide MeSH Prohlížeč

A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure-activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.

• Klíčová slova
• 3D-QSAR, CoMSA, MTT assay, PET inhibition, X-Ray structure, antimycobacterial activity, antistaphylococcal activity, cytotoxicity, hydroxynaphthalenecarboxamides, lipophilicity,
• MeSH
• ampicilin farmakologie   MeSH
• analýza hlavních komponent MeSH
• anilidy chemická syntéza   chemie   farmakologie   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• chloroplasty účinky léků   fyziologie   MeSH
• fotosyntéza účinky léků   MeSH
• isoniazid farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   růst a vývoj   MeSH
• metylace MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium kansasii účinky léků   růst a vývoj   MeSH
• Mycobacterium tuberculosis účinky léků   růst a vývoj   MeSH
• naftoly chemická syntéza   chemie   farmakologie   MeSH
• Spinacia oleracea chemie   účinky léků   metabolismus   MeSH
• THP-1 buňky MeSH
• transport elektronů účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• ampicilin MeSH
• anilidy MeSH
• antibakteriální látky MeSH
• isoniazid MeSH
• naftoly MeSH

: A series of sixteen ring-substituted N-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra, Fusarium avenaceum, and Bipolaris sorokiniana. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains and against M.tuberculosis. These compounds showed an activity against biofilm formation of S.aureus ATCC 29213 in concentrations close to MICs and an ability to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin, and tetracycline). In time-kill studies, a decrease of CFU/mL of >99% after 8 h from the beginning of incubation was observed. (2E)-N-(3,5-Dichlorophenyl)- and (2E)-N-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 µM against M. tuberculosis, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2E)-N-(3-Fluorophenyl)- and (2E)-N-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 µM, respectively, against B. sorokiniana. The screening of the cytotoxicity of the most effective antimicrobial compounds was performed using THP-1 cells, and these chosen compounds did not shown any significant lethal effect. The compounds were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. (2E)-N-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC50 = 5.1 µM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against Nicotiana tabacum var. Samsun. The structure⁻activity relationships are discussed.

• Klíčová slova
• MTT assay, PET inhibition, antifungal activity, antistaphylococcal activity, antitubercular activity, biofilm, cinnamamides, structure–activity relationship, time-kill assay, toxicity,
• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• antituberkulotika chemická syntéza   chemie   farmakologie   MeSH
• biofilmy účinky léků   MeSH
• cinnamáty chemická syntéza   chemie   farmakologie   MeSH
• Fusarium účinky léků   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   fyziologie   MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium tuberculosis účinky léků   fyziologie   MeSH
• nemoci rostlin mikrobiologie   MeSH
• rostliny mikrobiologie   MeSH
• stafylokokové infekce farmakoterapie   MeSH
• Staphylococcus aureus účinky léků   fyziologie   MeSH
• techniky syntetické chemie MeSH
• tuberkulóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• antituberkulotika MeSH
• cinnamamide MeSH Prohlížeč
• cinnamáty MeSH

Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC50 = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed.

• Klíčová slova
• hydroxynaphthalene-carboxamides, photosynthetic electron transport (PET) inhibition, spinach chloroplasts, structure-activity relationships,
• MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• fotosyntéza účinky léků   MeSH
• fotosystém II (proteinový komplex) metabolismus   MeSH
• inhibiční koncentrace 50 MeSH
• naftoly * chemická syntéza   chemie   farmakologie   MeSH
• Spinacia oleracea účinky léků   metabolismus   MeSH
• transport elektronů účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fotosystém II (proteinový komplex) MeSH
• naftoly * MeSH

Eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC50 values ranged from 0.05 to 0.664 mmol/L; and the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl)-carbamoyl]naphthalen-2-yl propylcarbamate. It has been proven that the compounds are PET-inhibitors in photosystem II. Despite rather low PET-inhibiting activities, primary structure-activity trends can be discussed.

• Klíčová slova
• PET inhibition, alkylcarbamates, hydroxynaphthalene-carboxamides, spinach chloroplasts, structure-activity relationships,
• MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• fotosyntéza účinky léků   MeSH
• inhibiční koncentrace 50 MeSH
• karbamáty chemie   farmakologie   MeSH
• Spinacia oleracea metabolismus   MeSH
• transport elektronů účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• karbamáty MeSH