Preparation and Photosynthesis-Inhibiting Activity of Novel Dihalogenated 3-Hydroxynaphthalene-2-carboxanilides

Abstract

In this study, a series of nine 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by fluorine, chlorine and bromine in various positions, was prepared by microwave-assisted synthesis and characterized. The compounds 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 within a wide range, but rather moderate; the highest activity within the series of the compounds was observed for N-(3,5-difluorophenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 9.8 µM). The compounds were found to inhibit PET in photosystem II.

Photosynthesis-Inhibiting Activity of Methoxy-Substituted 3-Hydroxynaphthalene-2-Carboxanilides

“…Due to the limited number of compounds, of which only 3 showed moderate activity, it is not possible to thoroughly evaluate the structure-activity relationships, it is not even possible to formulate trends, see Figure 1A,B, where the dependence of the PET-inhibiting activity expressed as log (1/IC50 [M]) of compounds 1-6 in spinach chloroplasts on lipophilicity (log p) and electronic σ(Ar) properties of the whole anilide substituents is plotted. On the other hand, these limited observations are fully consistent with recently published results [23,28,29]. The position of anilide substitution is critical; the disubstitution of both meta positions, i.e., C(3)' and C(5)', is more preferred for higher PETinhibiting activity and gives more active compounds than mono-meta-substitutions [23,28,29].…”

“…On the other hand, these limited observations are fully consistent with recently published results [23,28,29]. The position of anilide substitution is critical; the disubstitution of both meta positions, i.e., C(3)' and C(5)', is more preferred for higher PETinhibiting activity and gives more active compounds than mono-meta-substitutions [23,28,29]. Any other combinations of positions led to a reduction or loss of PET inhibition [23,28,29].…”

“…All the studied compounds were prepared according to Scheme 1 as described previously by Kos et al [21,23,24]. The condensation of 3-hydroxynaphthalene-2-carboxylic acid with appropriate substituted anilines using phosphorus trichloride in dry chlorobenzene under microwave conditions gave a series of target 3-hydroxy-N-arylnaphthalene-2-carboxanilides 1-6, see Table 1 Scheme 1.…”

“…Since monosubstituted derivatives of 3hydroxy-N-arylnaphthalene-2-carboxanilides showed PET inhibition in spinach chloroplasts (Spinacia oleracea L.), selected new derivatives variously substituted by dimethoxy, fluoro-methoxy or chloro-methoxy groups were evaluated for their PET-inhibiting activity. Thus, this short paper builds on the previous work [21,23,[25][26][27][28][29][30][31][32][33] aimed at investigating the PET-inhibiting activity of naphthalenecarboxamides. The relationships between structure and activity are briefly discussed.…”

“…A series of ring-monosubstituted anilides of 3-hydroxynaphtalene-2-carboxylic acid were published by Kos et al [21,22] as compounds with an interesting spectrum of biological activities. Recently, disubstituted derivatives [23,24] have been published. Since monosubstituted derivatives of 3hydroxy-N-arylnaphthalene-2-carboxanilides showed PET inhibition in spinach chloroplasts (Spinacia oleracea L.), selected new derivatives variously substituted by dimethoxy, fluoro-methoxy or chloro-methoxy groups were evaluated for their PET-inhibiting activity.…”