Bioprospection of Phytotoxic Plant-Derived Eudesmanolides and Guaianolides for the Control of Amaranthus viridis, Echinochloa crus-galli, and Lolium perenne Weeds

Abstract

The phytotoxicities of a selection of eudesmanolides and guaianolides, including natural products and new derivatives obtained by semisynthesis from plant-isolated sesquiterpene lactones, were evaluated in bioassays against three weeds of concern in agriculture (Amaranthus viridis L., Echinochloa crus-galli L., and Lolium perenne L.). Both eudesmanolides and guaianolides were active against the root and shoot growth of all the species, with the eudesmanolides generally showing improved activities. The IC₅₀ values obtained for the herbicide employed as positive control (on root and shoot growth, respectively, A. viridis: 27.8 and 85.7 μM; E. crus-galli: 167.5 and 288.2 μM; L. perenne: 99.1 and 571.4 μM) were improved in most of the cases. Structure-activity relationships were discussed, finding that hydroxylation of the A-ring and C-13 as well as the position, number, and orientation of the hydroxyl groups and the presence of an unsaturated carbonyl group can significantly influence the level of phytotoxicity. γ-Cyclocostunolide was the most active compound in the series, followed by others such as dehydrozaluzanin C and α-cyclocostunolide (outstanding their IC₅₀ values on A. viridis)─natural products that can therefore be suggested as models for herbicide development if further research indicates effectiveness on a larger scale and environmental safety in ecotoxicological assessments.

Keywords: bioassays; herbicide development models; phytotoxicity studies; sesquiterpene lactones; structure−activity relationships; weed control.

Figure 1

General structures of the compounds studied and that of the guaianolide dehydrocostuslactone (10).

Figure 2

Eudesmanolides (1–9) and guaianolides (11–18) tested in the phytotoxicity bioassays: βcyclocostunolide (1), 3α-hydroxy-β-cyclocostunolide (2), 11α-hydroxymethyl-β-cyclocostunolide (3), αcyclocostunolide (4), 11α-hydroxymethyl-α-cyclocostunolide (5), 3-deoxybrachylaenolide (6), 11αhydroxymethyl-3-deoxybrachylaenolide (7), 5α-hydroxy-3-deoxybrachylaenolide (8), γ-cyclocostunolide (9), zaluzanin C (11), isozaluzanin C (12), 5α-hydroxydehydrocostuslactone (13), 5α-hydroxyisozaluzanin C (14), 1α,5α-dihydroxyisozaluzanin C (15), 11α-hydroxymethyldehydrocostuslactone (16), 11α-(2-hydroxypropyl)dehydrocostuslactone (17), and dehydrozaluzanin C (18).

Figure 3

Preparation of β-cyclocostunolide (1), α-cyclocostunolide (4), γ-cyclocostunolide (9), and 3-deoxybrachylaenolide (6) from costunolide.

Figure 4

Reactions applied to eudesmanolides 1, 4, 6, and 9 to obtain hydroxylated derivatives in the A-ring (left column) and at C-13 (right column).

Figure 5

Synthesis of guaianolides 11–15 and dehydrozaluzanin C (18).

Figure 6

Synthesis of the hydroxylated derivatives of DHC at C-13 (16) and C-16 (17).

Figure 7

Phytotoxicity profiles obtained for eudesmanolides 1–9, guaianolides 11–18, and the positive control (Logran) in the etiolated wheat coleoptile bioassay. Positive values indicate stimulation of growth vs the negative control and negative values indicate inhibition. Error bars represent the standard error of the mean.

Figure 8

Cluster analysis of the phytotoxicity of compounds 1–9, 11–18, and the herbicide Logran (positive control) against Amaranthus viridis, Echinochloa crus-galli, and Lolium perenne growth.

Figure 9

Phytotoxicity of eudesmanolides 1–9, guaianolides 11–18, and the herbicide Logran (positive control) against the root and shoot growth of Amaranthus viridis. Positive values indicate stimulation of growth vs the negative control, and negative values indicate inhibition. Significance levels: p < 0.01 (a), or 0.01 < p < 0.05 (b). Error bars represent the standard error of the mean.

Figure 10

Phytotoxicity of eudesmanolides 1–9, guaianolides 11–18, and the herbicide Logran (positive control) against the root and shoot growth of Echinochloa crus-galli. Positive values indicate stimulation of growth vs the negative control, and negative values indicate inhibition. Significance levels: p < 0.01 (a), or 0.01 < p < 0.05 (b). Error bars represent the standard error of the mean.

Figure 11

Phytotoxicity of eudesmanolides 1–9, guaianolides 11–18, and the herbicide Logran (positive control) against the root and shoot growth of Lolium perenne. Positive values indicate stimulation of growth vs the negative control, and negative values indicate inhibition. Significance levels: p < 0.01 (a), or 0.01 < p < 0.05 (b). Error bars represent the standard error of the mean.

Figure 12

Graphs providing molecular descriptors for the most active compounds: (A) molecular weight; (B) Clog P, partition coefficient; (C) number of hydrogen bond acceptors; and (D) number of hydrogen bond donors. Red and green lines respectively indicate the minimum (min) and maximum (max) values found for commercially available herbicides.^,