Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic Electron Transport in Photosystem II

Abstract

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.

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

“…On the other hand, it is evident that PET-inhibiting activity increased linearly with an increase of the log P values within a series of chlorinated derivatives 4-7 (correlation coefficient r = 0.9628, n = 4), see Figure 1A, while decreasing linearly with an increase of the electron-withdrawing properties of the anilide ring (correlation factor r = 0.9284, n = 4), see Figure 1B, which influences the electron density on the CONH moiety, resulting in the ability of the amide bond to interact with enzymatic systems. A dependence of PET inhibition on the electron-withdrawing effect of substituents in individual series of many PET inhibitors was observed [9,17,[19][20][21][22]24,25]. The disubstitution of the anilide ring on positions C(3,5)', i.e., on both meta positions, is the most advantageous for high PET inhibition.…”

“…A series of 3-hydroxy-N-arylnaphthalene-2-carboxanilides monosubstituted on the anilide ring was prepared and published recently [17,18]. As the observed PET inhibition by these compounds in spinach chloroplasts (Spinacia oleracea L.) was moderate and inspired by the high PET-inhibiting activity of halogenated 1-hydroxynaphthalene-2-carboxanilides [19], a new series of 3-hydroxy-N-arylnaphthalene-2-carboxanilides disubstituted by fluorine, chlorine, or bromine on the anilide nucleus was designed to increase PET activity. Thus, this short contribution is a follow-up work to the previous papers [9,17,[19][20][21][22][23][24][25][26][27] aimed at the investigation of the PET-inhibiting activity of (aza)naphthalenecarboxamides.…”

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

“…Ring-substituted N-arylcinnamanilides were recently synthesized and tested for their antibacterial, antimycobacterial, and antifungal activity as well as for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts [10,11]. These compounds were designed based on the excellent experience with naphthalenecarboxamides-simple molecules with a number of biological activities, and in fact, ring-substituted (2E)-N-aryl-3-phenylprop-2-enamides can be considered as open or radical analogues of described naphthalene-2-carboxanilides [12][13][14][15][16][17] characterized by high spatial flexibility and solubility, see Figure 1. Since N-phenylcinnamamide skeleton can be considered as a privileged scaffold providing multi-target agents, new anilide halogenated derivatives were prepared.…”

Preparation and Hydro-Lipophilic Properties of Methoxylated and Methylated 1-Hydroxynaphthalene-2-Carboxanilides

“…Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were recently synthesized and tested for their antibacterial and antimycobacterial activity, as well as for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts [10][11][12][13].…”

“…The new methoxy and methyl multisubstituted derivatives expand the spectrum of substitutions in the carboxanilide part of the molecule. As it was found that the lipophilicity of these significantly biologically-effective agents [10][11][12][13] determines their activity, this study investigated and compared the hydro-lipophilic properties of new methoxy and methyl multisubstituted 1-hydroxynaphthalene-2-carboxanilides with the hydro-lipophilic properties of recently-prepared monosubstituted Nalkoxy-1-hydroxy-naphthalene-2-carboxanilides and N-alkyl-1-hydroxy-naphthalene-2carboxanilides. This contribution is a follow-up work to the previous papers [5-9; 14-24] aimed at the investigation of the physicochemical properties of new, biologically-active agents.…”