Preparation and Biological Properties of Ring-Substituted Naphthalene-1-Carboxanilides

Abstract

Abstract: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.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 -[4-(trifluoromethyl)phenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed.

The Structure&ndash;Photosynthesis-Inhibiting Activity Relationships of the Compounds Containing the <em>N</em>-Arylpiperazine Moiety

“…The positive influence of the 3´-CF3 group, which was attached to the phenylcarbamoyl moiety of tested 1-hydroxynaphthalene-2-carboxanilides (Figure 2a), on the PET inhibition was also observed [29]. The position changing of that lipophilic group on the phenylcarbamoyloxy fragment (4´-CF3) of structurally similar naphthalene-1-carboxanilides ( Figure 2b) was concerned favorable [30] as well. On the other hand, the PET-inhibiting activity of 8-hydroxyquinoline-2-carboxanilides ( Figure 2c) decreased as follows: 3´-CF3 substituted derivative  2´-CF3 substituted derivative  4´-CF3 substituted derivative [18].…”

Preparation and Hydro-Lipophilic Properties of Selected Novel Chlorinated and Brominated N-Arylcinnamamides

“…Regarding these observations, it should be noted that the programs cannot always exactly calculate the lipophilicity contribution of substituents in ortho positions, e.g., in this case due to spatially close carboxamide linker [10,12,16,[18][19][20] (see compounds 7/2 or 4/6 when evaluated 2-Br-4-Cl (7) was less lipophilic than 2,4-Cl (2) and, to the contrary, disubstituted 3-Cl-4-Br (6) was more lipophilic than trisubstituted 2,4,5-Cl (4)). These facts are caused by intramolecular interactions that can be observed just for ortho substituents/substitutions [10,12,16,[18][19][20]21]. Distributive parameters π describe the lipophilicity contribution of individual moieties substituted in some skeleton [22,23].…”

“…Note, based on the previous experience [10,12,16,[18][19][20], it can be supposed that once anilide is substituted by fluorine or trifluoromethyl moieties (still within halogene substituents), only experimentally determined log k values specify well the lipophilicity of the compounds due to strong intra-and intermolecular interactions of these specific substituents with the rest of pattern molecule or with the second compound or with medium.…”

Preparation and Photosynthesis-Inhibiting Activity of <em>N</em>-(n-Alkoxy)phenylamides of 2-Hydroxynaphthalene-1-carboxylic acid

“…Although at present approximately 20 mechanisms of action of herbicides are known [16], over 50% of commercially available herbicides act by reversible binding to photosystem II (PS II), a membrane-protein complex in the thylakoid membranes, which catalyses the oxidation of water and the reduction of plastoquinone [17], and thereby inhibit photosynthesis [18][19][20]. Some organic compounds, possessing an amide (-NHCO-) group, e.g., substituted anilides [5][6][7][8][11][12][13][14][15]21,22], were found to interact with tyrosine radicals Tyr Z and Tyr D (or their surroundings) which are situated in D 1 and D 2 proteins on the donor side of PS II. Due to this interaction, interruption of the photosynthetic electron transport occurs.…”

“…Due to this interaction, interruption of the photosynthetic electron transport occurs. In the context of the previously-described amides/carbamates [4][5][6][7][8][9][10][11][12][13][14][15]21,22], new N-(n-alkoxy)phenylamides of 2-hydroxynaphthalene-1-carboxylic acid were prepared and tested for their photosynthesis-inhibiting activity -the inhibition of photosynthetic electron transport in spinach chloroplasts (Spinacia oleracea L.). The 2-hydroxynaphthalene-1-carboxanilides can be considered as cyclic analogues of above discussed salicylanilides.…”