Synthesis of Rubrolide Analogues as New Inhibitors of the Photosynthetic Electron Transport Chain

Abstract

Many natural products have been used as a model for the development of new drugs and agrochemicals. Following this strategy 11 rubrolide analogues, bearing electron-withdrawing and -donating groups at both benzene rings, were prepared starting from commercially available mucobromic acid. The ability of all compounds to inhibit the photosynthetic electron transport chain in the chloroplast was investigated. The rubrolide analogues were effective in interfering with the light-driven ferricyanide reduction by isolated chloroplasts. The IC(50) values of the most active derivatives are in fact only 1 order of magnitude higher than those of commercial herbicides sharing the same mode of action, such as Diuron (0.27 μM). QSAR studies indicate that the most efficient compounds are those having higher ability to accept electrons, either by a reduction process or by an electrophilic reaction mechanism. The results obtained suggest that the rubrolide analogues represent promising candidates for the development of new active principles targeting photosynthesis to be used as herbicides.

Voltammetric and Theoretical Study of the Redox Properties of Rubrolide Analogues

“…The 1 H and 13 C NMR spectra were recorded on a Varian Mercury 300 spectrometer at 300 and 75 MHz, respectively, using CDCl 3 as solvent and TMS as internal reference, unless otherwise stated. Spectroscopic assignments for compounds 5-15 agreed with those reported in the literature [17]. The experimental details for the synthesis of compounds 16-35 are the same as reported previously [17].…”

“…Compounds 5-35 were prepared employing a procedure reported previously [17,19]. Melting points are uncorrected and were obtained from an MQAPF-301 melting point apparatus (Microquimica, Brazil).…”

“…1), secondary metabolites produced by marine ascidians [14][15][16][17]. All the synthetic analogues were able to interfere with the chloroplast electron transport chain and the most active compound showed an IC 50 (concentration causing 50% inhibition) value of 1.1 ± 0.2 M, only one order of magnitude higher than that of the commercial herbicide Diuron (0.27 M) [17]. These findings clearly suggest that rubrolide analogues may constitute promising lead structures for the development of new active molecules.…”

“…These findings clearly suggest that rubrolide analogues may constitute promising lead structures for the development of new active molecules. QSAR (quantitative structure-activity relationship) studies suggested a relationship between the biological activity and the redox potential of such molecules [17]. The most active compounds were those with higher ability to accept electrons, either by reduction or by an electrophilic reaction mechanism.…”

Recent developments on nano-ZnO catalyzed synthesis of bioactive heterocycles

“…Heterocyclic moieties are very common in naturally occurring compounds and are important because of their significant biological efficacies that include anticancer [3], cytotoxic [4], anti-malarial [5], anti-microbial [6], anti-inflammatory [7], anti-oxidant 1 3 [8] and many more [9,10]. Figure 1 represents a glimpse of marketed drugs containing heterocycles as the core structural unit [11][12][13][14][15][16].…”