- Investigation of hydro-lipophilic properties of n-alkoxyphenylhydroxynaphthalenecarboxamides ?
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The evaluation of the lipophilic characteristics of biologically active agents is indispensable for the rational design of ADMET-tailored structure–activity models. N-Alkoxy-3-hydroxynaphthalene-2-carboxanilides, N-alkoxy-1-hydroxynaphthalene-2-carboxanilides, and N-alkoxy-2-hydroxynaphthalene-1-carboxanilides were recently reported as a series of compounds with antimycobacterial, antibacterial, and herbicidal activity. As it was found that the lipophilicity of these biologically active agents determines their activity, the hydro-lipophilic properties of all three series were investigated in this study. All 57 anilides were analyzed using the reversed-phase high-performance liquid chromatography method for the measurement of lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, a range of software lipophilicity predictors for the estimation of clogP values of a set of N-alkoxyphenylhydroxynaphthalenecarboxamides was employed and subsequently cross-compared with experimental parameters. Thus, the empirical values of lipophilicity (logk) and the distributive parameters (π) were compared with the corresponding in silico characteristics that were calculated using alternative methods for deducing the lipophilic features. To scrutinize (dis)similarities between the derivatives, a PCA procedure was applied to visualize the major differences in the performance of molecules with respect to their lipophilic profile, molecular weight, and violations of Lipinski’s Rule of Five.
- Kapustikova, Iva,Bak, Andrzej,Gonec, Tomas,Kos, Jiri,Kozik, Violetta,Jampilek, Josef
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- Antimycobacterial N-alkoxyphenylhydroxynaphthalenecarboxamides affecting photosystem II
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N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides (series A) and N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides (series B) affecting photosystem (PS) II inhibited photosynthetic electron transport (PET) in spinach chloroplasts. Their inhibitory activity depended on the compound lipophilicity as well as on the position of the alkoxy substituent. The most potent PET inhibitors were 2-hydroxy-N-phenylnaphthalene-1-carboxamide and N-[3-(but-2-yloxy)phenyl]-2-hydroxynaphthalene-1-carboxamide within series A (IC50?=?28.9 and 42.5?μM, respectively) and 1-hydroxy-N-(3-propoxyphenyl)naphthalene-2-carboxamide and 1-hydroxy-N-(3-ethoxyphenyl)-naphthalene-2-carboxamide (IC50?=?2.0 and 3.1?μM, respectively) within series B. The inhibitory activity of C′(3) or C′(4) alkoxy substituted compounds of series B was considerably higher than that of C′(2) ones within series A. The PET-inhibiting activities of both series were compared with the PET inhibition of isomeric N-alkoxyphenyl-3-hydroxynaphthalene-2-carboxamides (series C) reported recently. 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.
- Gonec, Tomas,Kralova, Katarina,Pesko, Matus,Jampilek, Josef
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p. 1881 - 1885
(2017/04/07)
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- N-alkoxyphenylhydroxynaphthalenecarboxamides and their antimycobacterial activity
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A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthes
- Gonec, Tomas,Pospisilova, Sarka,Kauerova, Tereza,Kos, Jiri,Dohanosova, Jana,Oravec, Michal,Kollar, Peter,Coffey, Aidan,Liptaj, Tibor,Cizek, Alois,Jampilek, Josef
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- Antibacterial and herbicidal activity of ring-substituted 2-hydroxynaphthalene-1-carboxanilides
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In this study, a series of twenty-two ring-substituted 2- hydroxynaphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant
- Gonec, Tomas,Kos, Jiri,Zadrazilova, Iveta,Pesko, Matus,Govender, Rodney,Keltosova, Stanislava,Chambel, Barbara,Pereira, Diogo,Kollar, Peter,Imramovsky, Ales,O'Mahony, Jim,Coffey, Aidan,Cizek, Alois,Kralova, Katarina,Jampilek, Josef
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p. 9397 - 9419
(2013/09/23)
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- Synthesis, antimicrobial, and QSAR studies of substituted benzamides
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A series of new substituted benzamides were synthesized and tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well for antifungal activity. The compounds 8i and 9 showed better activity among the different benzamides synthesized. The structural characteristics governing antibacterial activities of substituted benzamides were studied using QSAR methodology. The results showed that the antimicrobial activity could be modeled using the topological descriptors, molecular connectivity indices (2χv and 2χ) and Kiers shape index (κα1). The low residual activity and high cross-validated r2 values (rcv2) observed indicated the predictive ability of the developed QSAR models.
- Kumar, Anil,Narasimhan, Balasubramanian,Kumar, Devinder
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p. 4113 - 4124
(2008/03/11)
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- Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxylic acids
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A facile method for the activation of hydroxy-substituted carboxylic acids using benzotriazole chemistry without prior protection of the hydroxy substituents is presented. The N-acylbenzotriazole intermediates 2a-g, 6a-d, and 9a-c have been used for high-yielding synthesis of both aliphatic (3a-1) and aromatic (7a-h, 10a-f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a-h and 13a-i were obtained using either neat alcohols in neutral microwave conditions or nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate yields were obtained in the case of aliphatic hydroxy esters 11a,b and thiolesters 11e-g from the intermediates 2a-c.
- Katritzky, Alan R.,Singh, Sanjay K.,Cai, Chunming,Bobrov, Sergey
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p. 3364 - 3374
(2007/10/03)
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