Carlos Rial

BACKGROUND: Cynaropicrin, the major sesquiterpene lactone in Cynara cardunculus leaves, exhibits phytotoxic activity and is a promising candidate for sustainable weed management. However, its environmental stability and the biological activity of its transformation products under agronomic and soil conditions remain poorly understood. This study investigated its stability under high temperature (50 °C) and pH (5 and 8), mimicking agronomic extremes, and under soil context. RESULTS: Cynaropicrin remained stable at 50 °C and pH 5 for up to 72 h but degraded extensively at pH 8, with an 80% concentration reduction over 7 days. Deacylcynaropicrin emerged as the major degradation product under alkaline conditions. In soil, complete degradation occurred within 7 days, producing dehydrocynaropicrin and a new compound, 4,15‐dihydro‐dehydrocynaropicrin. Bioassays demonstrated that both degradation products exhibited higher phytotoxic activity against P. oleracea than cynaropicrin and deacylcynaropicrin. CONCLUSION: This research is the first to highlight cynaropicrin's stability, characterize the structures of its degradation products, and their phytotoxicity, showing the strong impact of environmental factors and microbes. The findings underscore its ecological importance and potential for sustainable weed control. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Aminophenoxazinones (APOs) are potent phytotoxic metabolites and histone deacetylase inhibitors, offering a low-resistance bioherbicide profile. This research synthesized a library of APO derivatives with targeted modifications to optimize physicochemical properties and biological activity using oxidative cyclocondensation. Purification challenges from strong compound-solid phase interactions were overcome by using centrifugal partition chromatography (CPC). Phytotoxicity was screened against Lolium rigidum, Portulaca oleracea, and Plantago lanceolata. While germination remained largely unaffected, compounds 10 and 11 caused significant root inhibition (77% and 89%, respectively for P. oleracea) at 1000 μM. Specifically, 11 reached inhibition levels comparable to the positive control, pendimethalin (86% for P. oleracea). Following a detailed structure-activity relationship analysis, 10 emerged as the most potent candidate, exhibiting an IC₅₀ of 4.5 μM against P. oleracea roots, considerably lower than that of natural APO (332.5 μM). These findings strongly validate this rational design and purification strategy, positioning 10 as a valuable agrochemical lead for sustainable weed management.

Background: A Cynara cardunculus leaf extract enriched in sesquiterpene lactones (CcLERSLs) exhibited strong phytotoxic activity, notably inhibiting weed root growth. However, the poor water solubility limits practical application. This study aimed to develop and optimize an oil‐in‐water nanoemulsion containing CcLERSLs, using grape seed oil as carrier, and pectin and Tween®80 as emulsifiers. Ultrasound‐assisted emulsification and response surface methodology were applied to optimize droplet size, stability and bioavailability. Phytotoxicity and storage stability were evaluated. Results: Models for droplet size and zeta‐potential identified ultrasound amplitude and Tween®80 content as significant variables, respectively. Model validation confirmed high predictive accuracy, particularly for droplet size, and this guided the formulation of the CcLERSLs nanoemulsion (5% w/w GSO, 4% Tween® 80, 1% pectin, 80% ultrasound amplitude). Phytotoxicity against Portulaca oleracea , Plantago lanceolata and Phalaris arundinacea showed a ≥3‐fold increase in activity compared with the crude extract, particularly for root inhibition. P. oleracea was the most sensitive and the nanoemulsion outperformed the commercial herbicide at 400–800 ppm. The nanoemulsion remained physically stable at 4 and 25 °C for 90 days but degraded significantly at 45° C. Conclusions: Nanoemulsion formulation enhances bioavailability of the CcLERSLs and significantly improves its phytotoxic activity, supporting its potential as a promising natural herbicide. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The negative implications for weeds encourage the finding of novel sources of phytotoxic agents for sustainable management. While traditional herbicides are effective, especially at large scales, the environmental impact and proliferation of resistant biotypes present major challenges that natural sources could mitigate. In this study, the potential of ginger metabolites as phytotoxic agents has been investigated for the first time. Root extracts, prepared via various extraction techniques, showed phytotoxicity in wheat (Triticum aestivum L. cv. Burgos) coleoptile bioassays at 800–100 ppm, and the most active extract (prepared by sonication with ethyl acetate) was purified by chromatographic methods, yielding seven compounds: five phenolic metabolites with gingerol and shogaol structures, β-sitosterol, and linoleic acid. Some of the major phenolic metabolites, especially [6]-shogaol and [6]-gingerol, exerted phytotoxicity on wheat coleoptiles, Plantago lanceolata and Portulaca oleracea (broadleaf dicotyledon weeds). This promoted the study of a collection of derivatives, revealing that the 5-methoxy, oxime, and acetylated derivatives of [6]-shogaol and [6]-gingerol had interesting phytotoxicities, providing clues for improving the stability of the isolated structures. Ginger roots have been demonstrated to be a promising source of bioactive metabolites for weed control, offering novel materials with potential for the development of agrochemicals based on natural products.

Sesquiterpene lactones (SLs) are compounds that are highly produced in Cynara cardunculus leaves, known for their phytotoxic activity. This study aims to assess SL-enriched fractions’ (cynaropicrin, aguerin B, and grosheimin) phytotoxic potentials and putative modes of action, compared to an initial extract, using two approaches: first, against a panel of nine weed species in pre-emergence, and then on Portulaca oleracea L.’s post-emergency stage. The SL-enriched fractions demonstrated greater phytotoxic activity when compared with the C. cardunculus leaf initial extract. The SL-enriched fractions had higher activity at root growth inhibition over the panel tested, doubling the activity in five of them at 800 ppm. Regarding the post-emergence bioassay, the SL-enriched fractions had a higher influence on the plants’ growth inhibition (67% at 800 ppm). The SL-effects on the plants’ metabolisms were evidenced. The total chlorophyll content was reduced by 65% at 800 ppm. Oxidative stress induction was observed because of the enhancement in MDA levels at 800 ppm compared to control (52%) and the decrease in SOD-specific activity from 4.20 U/mg protein (400 ppm) to 1.74 U/mg protein (800 ppm). The phytotoxic effects of the SL-enriched fractions suggest that they could be used for a future bioherbicide development.

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.

A study proposing cyclodextrins as eco-friendly compounds to enhance the physicochemical properties of phthalimide-lactones to produce complexes inducing the germination of parasitic weeds even without using organic co-solvents.

Natural products have been postulated as an alternative to the use of synthetic herbicides in pest control. The latter compounds have caused numerous problems and these include the appearance of resistance to such herbicides. Aminophenoxazinones are natural products that have shown multiple biological activities, such as pharmacological or phytotoxic effects. In the case of phytotoxicity, the mode of action of aminophenoxazinones has not been widely exploited in agriculture and resistant weeds have not been reported to date. This fact makes aminophenoxazinones promising candidates in the development of herbicides. In the study reported here, seven aminophenoxazinone derivatives have been synthesized and their phytotoxicity has been evaluated on wheat coleoptiles and two important agricultural weeds (Lolium rigidum and Portulaca oleracea). Several derivatives have shown phytotoxic activity, which is similar to the positive control pendimethalin, and even higher in some cases at the highest concentrations tested. The most affected parameter in weeds was root length and the most susceptible weed was P. oleracea. Compound 2, in which nitrogen atoms are present in the heterocycles, was the most active and this was followed by compound 1. Modifications at C-8 led to a reduced activity, with the exception of the nitro compound on the root length of P. oleracea. However, the phytotoxicity also increased on introducing an iodo-substituent at C-4. The results highlight aminophenoxazinones as promising candidates in the development of natural herbicides.

BACKGROUND: Natural products are a promising source for the development of new pesticides with alternative mechanisms of action. In this study, we evaluated the phytotoxic and antifungal activity of a novel family of natural C₁₇‐sesquiterpenoids and performed a study of the effect caused by the elimination of the α‐methylene‐γ‐butyrolactone system and its importance to their biological activity.RESULTS: Many tested compounds exhibited a strong phytotoxic activity. Lappalone and pertyolide B were the most potent molecules from the tested group. Lappalone displayed a strong inhibition profile against selected weed species, reaching a half‐maximal inhibitory concentration (IC₅₀) value of 5.0 μm against Echinochloa crus‐galli L. shoot and 5.7 μm against the germination rate of Amaranthus viridis L., as well as a good stimulation of the germination of Phelipanche ramosa L. Pertyolide B demonstrated excellent inhibition against Amaranthus viridis L. (IC₅₀: 56.7, 70.3 and 24.0 μm against the root and shoot growth, and germination rate, respectively) and Allium cepa L. (representative of the Liliaceae family, with IC₅₀ values of 25.3 and 64.4 μm against root and shoot growth). Regarding the antifungal activity, pertyolide B presented significant activity against Colletotrichum fragareae and Fusarium oxysporum with a minimum inhibitory concentration of 6.6 μg μL⁻¹.CONCLUSION: The bioassays revealed that frequently the presence of the α‐methylene‐γ‐butyrolactone system is not essential for the bioactivities of sesquiterpene lactones, and suggest that C₁₇‐sesquiterpenoids may function through a different mechanism of action not related to the widely assumed Michael addition. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The encapsulation of bioactive natural products has emerged as a relevant tool for modifying the poor physicochemical properties often exhibited by agrochemicals. In this regard, natural guaiane-type sesquiterpene lactones isolated from Cynara cardunculus L. have been encapsulated in a core/shell [email protected] system. Monitoring of the F and O signals in marked sesquiterpenes confirmed that the compound is present in the nanotube cavity. These structures were characterized using scanning transmission electron microscopy–X-ray energy-dispersive spectrometry techniques, which revealed the spatial layout relationship and confirmed encapsulation of the sesquiterpene lactone derivative. In addition, biological studies were performed with aguerin B (1), cynaropicrin (2), and grosheimin (3) on the inhibition of germination, roots, and shoots in weeds (Phalaris arundinacea L., Lolium perenne L., and Portulaca oleracea L.). Encapsulation of lactones in nanotubes gives better results than those for the nonencapsulated compounds, thereby reinforcing the application of fully organic nanotubes for the sustainable use of agrochemicals in the future.