A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.

• Keywords
• Michael acceptors, antimicrobial activity, cinnamamides, cytotoxicity, docking study, lipophilicity, structure–activity relationships,
• MeSH
• Anti-Bacterial Agents pharmacology   chemistry   MeSH
• Cinnamates pharmacology   chemistry   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus * MeSH
• Microbial Sensitivity Tests MeSH
• Staphylococcal Infections * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Cinnamates MeSH
• cinnamic acid MeSH Browser

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.

• Keywords
• PET inhibition, hydroxynaphthalene-carboxamides, spinach chloroplasts, structure-activity relationships,
• MeSH
• Chloroplasts drug effects   metabolism   MeSH
• Photosynthesis drug effects   MeSH
• Photosystem II Protein Complex antagonists & inhibitors   metabolism   MeSH
• Herbicides chemistry   metabolism   MeSH
• Naphthalenes chemistry   metabolism   MeSH
• Spinacia oleracea drug effects   metabolism   MeSH
• Electron Transport drug effects   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Photosystem II Protein Complex MeSH
• Herbicides MeSH
• Naphthalenes MeSH

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.

• Keywords
• 3D-QSAR, CoMSA, MTT assay, PET inhibition, X-Ray structure, antimycobacterial activity, antistaphylococcal activity, cytotoxicity, hydroxynaphthalenecarboxamides, lipophilicity,
• MeSH
• Ampicillin pharmacology   MeSH
• Principal Component Analysis MeSH
• Anilides chemical synthesis   chemistry   pharmacology   MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Chloroplasts drug effects   physiology   MeSH
• Photosynthesis drug effects   MeSH
• Isoniazid pharmacology   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   growth & development   MeSH
• Methylation MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium kansasii drug effects   growth & development   MeSH
• Mycobacterium tuberculosis drug effects   growth & development   MeSH
• Naphthols chemical synthesis   chemistry   pharmacology   MeSH
• Spinacia oleracea chemistry   drug effects   metabolism   MeSH
• THP-1 Cells MeSH
• Electron Transport drug effects   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Ampicillin MeSH
• Anilides MeSH
• Anti-Bacterial Agents MeSH
• Isoniazid MeSH
• Naphthols 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.

• Keywords
• MTT assay, PET inhibition, antifungal activity, antistaphylococcal activity, antitubercular activity, biofilm, cinnamamides, structure–activity relationship, time-kill assay, toxicity,
• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Antifungal Agents chemical synthesis   chemistry   pharmacology   MeSH
• Antitubercular Agents chemical synthesis   chemistry   pharmacology   MeSH
• Biofilms drug effects   MeSH
• Cinnamates chemical synthesis   chemistry   pharmacology   MeSH
• Fusarium drug effects   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   physiology   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium tuberculosis drug effects   physiology   MeSH
• Plant Diseases microbiology   MeSH
• Plants microbiology   MeSH
• Staphylococcal Infections drug therapy   MeSH
• Staphylococcus aureus drug effects   physiology   MeSH
• Chemistry Techniques, Synthetic MeSH
• Tuberculosis drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antifungal Agents MeSH
• Antitubercular Agents MeSH
• cinnamamide MeSH Browser
• Cinnamates MeSH

Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure-inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3'-/4'-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.

• Keywords
• CoMSA, IVE-PLS, carbamates, in vitro cholinesterase inhibition, in vitro cytotoxicity assay, molecular docking study, proline,
• MeSH
• Acetylcholinesterase chemistry   MeSH
• Butyrylcholinesterase chemistry   MeSH
• Cholinesterase Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Carbamates chemical synthesis   chemistry   pharmacology   MeSH
• Catalytic Domain MeSH
• Molecular Conformation MeSH
• Proline * chemistry   MeSH
• Molecular Docking Simulation MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholinesterase MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors MeSH
• Carbamates MeSH
• Proline * 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.

• Keywords
• hydroxynaphthalene-carboxamides, photosynthetic electron transport (PET) inhibition, spinach chloroplasts, structure-activity relationships,
• MeSH
• Chloroplasts drug effects   metabolism   MeSH
• Photosynthesis drug effects   MeSH
• Photosystem II Protein Complex metabolism   MeSH
• Inhibitory Concentration 50 MeSH
• Naphthols * chemical synthesis   chemistry   pharmacology   MeSH
• Spinacia oleracea drug effects   metabolism   MeSH
• Electron Transport drug effects   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Photosystem II Protein Complex MeSH
• Naphthols * MeSH

Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal on the environment. In this paper, we aimed to evaluate in vitro cytotoxic effects of five extracts prepared from P. magnifica using LDH assay on THP-1 cell line. Antimicrobial activities of extracts against 22 different bacterial strains were tested by microdilution method. Our study showed that all extracts tested, except aqueous portion, demonstrated LD50 values below 100 μg/mL, which indicates potential toxicity. The water extract of P. magnifica with LD50 value of 250 μg/mL also shows potentially harmful effects. Also, an environmental risk resulting from the presence and increasing biomass of potentially toxic benthic cyanobacteria in old colonies should not be underestimated. Toxicity of Pectinatella extracts could be partially caused by presence of Aeromonas species in material, since we found members of these genera as most abundant bacteria associated with P. magnifica. Furthermore, P. magnifica seems to be a promising source of certain antimicrobial agents. Its methanolic extract, hexane, and chloroform fractions possessed selective inhibitory effect on some potential pathogens and food spoiling bacteria in the range of MIC 0.5-10 mg/mL. Future effort should be made to isolate and characterize the content compounds derived from P. magnifica, which could help to identify the substance(s) responsible for the toxic effects of P. magnifica extracts.

• Keywords
• Aeromonas, Bryozoa, Pectinatella magnifica, antimicrobial activity, bacteria, cyanobacteria, invasive species, toxicity,
• MeSH
• Aeromonas chemistry   MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Bacteria drug effects   MeSH
• Bacterial Toxins pharmacology   MeSH
• Bryozoa chemistry   microbiology   MeSH
• Cell Line MeSH
• Chloroform pharmacology   MeSH
• Hexanes pharmacology   MeSH
• Humans MeSH
• Methanol pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Toxicity Tests MeSH
• Cell Survival drug effects   MeSH
• Introduced Species MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Bacterial Toxins MeSH
• Chloroform MeSH
• Hexanes MeSH
• Methanol MeSH

A series of twelve 2-[(E)-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-[(E)-2-(4-Methoxyphenyl)ethenyl]-1,3-benzoxazole, 2-[(E)-2-(2,3-dihydro-1-benzofuran-5-yl)ethenyl]-1,3-benzoxazole and 2-{(E)-2-[4-(methylsulfanyl)phenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E)-2-(2-methoxyphenyl)ethenyl]-1,3-benzoxazole was IC₅₀ = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed.

• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Benzoxazoles chemical synthesis   chemistry   pharmacology   MeSH
• Chloroplasts metabolism   MeSH
• Species Specificity MeSH
• Photosynthesis drug effects   MeSH
• Inhibitory Concentration 50 MeSH
• Mycobacteriaceae drug effects   MeSH
• Spinacia oleracea MeSH
• Electron Transport drug effects   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Benzoxazoles MeSH

In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenyl)naphthalene-1-carboxamide, N-(3-methoxy-phenyl)naphthalene-1-carboxamide, N-(3-methylphenyl)naphthalene-1-carboxamide, N-(4-methylphenyl)naphthalene-1-carboxamide and N-(3-fluorophenyl)naphthalene-1-carboxamide showed against M. avium subsp. paratuberculosis two-fold higher activity than rifampicin and three-fold higher activity than ciprofloxacin. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The testing of biological activity of the compounds was completed with the study of photosynthetic electron transport (PET) inhibition in isolated spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity expressed by IC50 value of the most active compound N-[4-(trifluoromethyl)phenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed.

• MeSH
• Anilides chemical synthesis   chemistry   pharmacology   MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Chloroplasts drug effects   metabolism   MeSH
• Photosynthesis drug effects   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   MeSH
• Naphthalenes chemistry   MeSH
• Spinacia oleracea drug effects   metabolism   MeSH
• Electron Transport drug effects   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anilides MeSH
• Anti-Bacterial Agents MeSH
• Naphthalenes 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
• Anti-Bacterial Agents chemical synthesis   pharmacology   MeSH
• Benzoates chemical synthesis   pharmacology   MeSH
• Carbamates chemical synthesis   pharmacology   MeSH
• Mycobacterium avium subsp. paratuberculosis drug effects   MeSH
• Uncoupling Agents chemical synthesis   pharmacology   MeSH
• Spinacia oleracea drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Benzoates MeSH
• Carbamates MeSH
• Uncoupling Agents MeSH