Effects of Phytotoxic Nonenolides, Stagonolide A and Herbarumin I, on Physiological and Biochemical Processes in Leaves and Roots of Sensitive Plants

Abstract

Phytotoxic macrolides attract attention as prototypes of new herbicides. However, their mechanisms of action (MOA) on plants have not yet been elucidated. This study addresses the effects of two ten-membered lactones, stagonolide A (STA) and herbarumin I (HBI) produced by the fungus Stagonospora cirsii, on Cirsium arvense, Arabidopsis thaliana and Allium cepa. Bioassay of STA and HBI on punctured leaf discs of C. arvense and A. thaliana was conducted at a concentration of 2 mg/mL to evaluate phenotypic responses, the content of pigments, electrolyte leakage from leaf discs, the level of reactive oxygen species, Hill reaction rate, and the relative rise in chlorophyll a fluorescence. The toxin treatments resulted in necrotic and bleached leaf lesions in the dark and in the light, respectively. In the light, HBI treatment caused the drop of carotenoids content in leaves on both plants. The electrolyte leakage caused by HBI was light-dependent, in contrast with that caused by STA. Both compounds induced light-independent peroxide generation in leaf cells but did not affect photosynthesis 6 h after treatment. STA (10 µg/mL) caused strong disorders in root cells of A. thaliana leading to the complete dissipation of the mitochondrial membrane potential one hour post treatment, as well as DNA fragmentation and disappearance of acidic vesicles in the division zone after 8 h; the effects of HBI (50 µg/mL) were much milder. Furthermore, STA was found to inhibit mitosis but did not affect the cytoskeleton in cells of root tips of A. cepa and C. arvense, respectively. Finally, STA was supposed to inhibit the intracellular vesicular traffic from the endoplasmic reticulum to the Golgi apparatus, thus interfering with mitosis. HBI is likely to have another main MOA, probably inhibiting the biosynthesis of carotenoids.

Structure–Activity Relationships of Natural C-9-Methyl-Substituted 10-Membered Lactones and Their Semisynthetic Derivatives

“…A new natural product, stagonolide L (1), obtained as a colorless oil that crystallizes while standing, has a molecular formula of C 10 H 14 O 5 , as deduced by HRESIMS (237.0733 [M + Na] + (calcd for C 10 H 14 O 5 Na, 237.0738)). The preliminary 1 H and 13 C NMR investigations showed that 1 is closely related to other 10-membered lactones previously isolated from different strains of S. cirsii. 6,7,9,10 Moreover, the IR spectrum of 1 indicated the presence of a hydroxyl group (3460 cm −1 ), an ester group (1741 cm −1 ), an additional keto group (1711 cm −1 ), and an epoxy C−O−C stretch (1023 cm −1 ).…”

“…Biological activity is known for some of these pairs and supports the hypothesis that the α,β-unsaturated carbonyl group (regardless of its position in the ring) is responsible for the overall toxicity of TMLs (Figure 6) and possibly other macrolides with a C-10−C-12 ring size. 12,13 According to the revealed SAR patterns, a wide spectrum of activity can be predicted for diplodialide A, 34 decarestrictine F, 35 and pyrenolides A and B, 16,36 the activity of which has not yet been studied.…”

“…Among the well-studied TMLs, these requirements are best met by herbarumin I. 7,8,12,13 Stagonolide A, which was used as an internal control in this study, is less attractive for herbicide development than herbarumin I owing to its nonselective toxicity. 7,12 Based on this study, curvulide A (4) is worth further consideration, since it demonstrates approximately the same level of phytotoxic activity with a little off-target toxicity (Table 2).…”

“…Infrared (IR) spectra were recorded on a KBr disc on an ALPHA FT-IR spectrometer (Bruker). 1 H and 13 C NMR spectra were recorded at 400 and 100 MHz, respectively, in CDCl 3 , using a Bruker AVANCE III 400 MHz spectrometer (Bruker). The solvent residual signal (δ7.26 ppm) for the 1 H NMR spectra and the carbon signal of CDCl 3 (δ 77.16 ppm) for the 13 C NMR spectra were used as references.…”

“…1 H and 13 C NMR spectra were recorded at 400 and 100 MHz, respectively, in CDCl 3 , using a Bruker AVANCE III 400 MHz spectrometer (Bruker). The solvent residual signal (δ7.26 ppm) for the 1 H NMR spectra and the carbon signal of CDCl 3 (δ 77.16 ppm) for the 13 C NMR spectra were used as references. DEPT, correlation spectroscopy (COSY)-45, nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiplequantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC) analyses were performed by using standard Bruker microprograms.…”