Sesquiterpene lactones from Tithonia diversifolia with ferroptosis-inducing activities.

Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

Guaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities.

Eight undescribed guaianolide sesquiterpene lactones cicholosumins A-H and twelve known ones were isolated from the aerial parts of Cichorium glandulosum Boiss et Huet. Their structures were established by 1D and 2D NMR spectroscopic data, electronic circular dichroism, quantum chemical calculations and single crystal X-ray diffraction analysis. Compounds 9α-hydroxy-3-deoxyzaluzanin C, epi-8α-angeloyloxycichoralexin, 8-O-methylsenecioylaustricin and lactucin showed strong anti-neuroinflammation activity with IC50 values of 1.69 ± 0.11, 1.08 ± 0.23, 1.67 ± 0.28 and 1.82 ± 0.27 µM, respectively. The mechanism research indicated that epi-8α-angeloyloxycichoralexin inhibited neuroinflammation through the NF-κB and MAPK pathways.

Effectiveness of Jena DM® Herbal Formulation as Complementary Therapy to Conventional Oral Hypoglycemic Agents in Type-2 Diabetes Mellitus: A Quasi-experimental Study.

BACKGROUND:  There is vast preclinical evidence that indicates that extracts from several Artemisia plant species have significant antidiabetic benefits. However, clinical evidence is limited to this effect. OBJECTIVE:  We sought to evaluate the effectiveness of Jena DM®  (an Artemisia annua-based poly-herbal formulation) on glycemic control (Hb A1C) and insulin metabolism (HOMA), when administered as a complementary therapy in type-2 diabetes mellitus (T2DM). This study was supported by a research grant (JRD005) from Jena Herbals (U) Ltd, which is a local herbal medicines manufacturing facility in Uganda. METHODS: We conducted a 12-week quasi-experimental study, involving 118 patients under routine follow-up at a diabetes and endocrinology clinic. Random assignment to either conventional or experimental study groups was done using a random number generator (Microsoft Excel version 16.0). Participant sociodemographic and clinical data as well as whole blood samples (3-5 mL) were obtained at scheduled clinic visits. Medication adherence was assessed using the Hill-Bone Scale, and adverse drug events (ADEs) using the Naranjo causality and the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) scales. Group differences in glycemic control (HbA1C), fasting serum insulin (FSI) indices (% HOMA2-B, HOMA-IR), and other cardiometabolic parameters were assessed using independent samples t-test, and Pearson chi-square statistical tests were used. A p-value <0.05 was considered statistically significant. Ethical approvals were obtained before the study commencement. RESULTS: 12-week daily complementary therapy with Jena DM®  showed no significant effect on Hb A1C reduction (0.1 (95% CI: -0.56, 0.80) %; p=0.798); however, we observed a significant reduction in total body weight (2.0 (95% CI: 0.73, 3.28) kg; p=0.002). The overall frequency of self-reported ADEs including dizziness was significantly higher among patients that used Jena DM®  (p=0.001). Epigastric pain was the most severe ADE necessitating clinical management. There was no significant difference in the homeostatic model assessment for insulin resistance (HOMA2-IR) between study groups. CONCLUSION:  In contrast to a few studies that previously showed significant hypoglycemic effects of Artemisia-based extracts, this study did not show a statistically significant reduction on HbA1C during a 12-week complementary use of Jena DM®  in patients with T2DM. Based on the findings of this study, future research should evaluate the long-term effects of Jena DM®  on body weight, overall insulin metabolism, and the subsequent effect on glycemic control in T2DM.

Discovery of sesquiterpene lactones with anti-inflammatory effect from Youngia japonica.

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

Recent advances in lycopene and germacrene a biosynthesis and their role as antineoplastic drugs.

Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A, and the tetraterpene, lycopene suffers supply chain deficits and poor yields, chemical synthesis has difficulties in separating stereoisomers. This review highlights cutting-edge developments in producing germacrene A and lycopene from microbial cell factories. We then summarize the antineoplastic properties of ß-elemene (a thermal product from germacrene A), sesquiterpene lactones (metabolic products from germacrene A), and lycopene. We also elaborate on strategies to optimize microbial-based germacrene A and lycopene production.

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.

Discovery of Sesquiterpene Lactones with Cytotoxicity from the Herb of Youngia japonica.

In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 µM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent.

Neuropsychopharmacological Induction of (Lucid) Dreams: A Narrative Review.

Lucid dreaming (LD) is a physiological state of consciousness that occurs when dreamers become aware that they are dreaming, and may also control the oneiric content. In the general population, LD is spontaneously rare; thus, there is great interest in its induction. Here, we aim to review the literature on neuropsychopharmacological induction of LD. First, we describe the circadian and homeostatic processes of sleep regulation and the mechanisms that control REM sleep with a focus on neurotransmission systems. We then discuss the neurophysiology and phenomenology of LD to understand the main cortical oscillations and brain areas involved in the emergence of lucidity during REM sleep. Finally, we review possible exogenous substances-including natural plants and artificial drugs-that increase metacognition, REM sleep, and/or dream recall, thus with the potential to induce LD. We found that the main candidates are substances that increase cholinergic and/or dopaminergic transmission, such as galantamine. However, the main limitation of this technique is the complexity of these neurotransmitter systems, which challenges interpreting results in a simple way. We conclude that, despite these promising substances, more research is necessary to find a reliable way to pharmacologically induce LD.

Britanin - a beacon of hope against gastrointestinal tumors?

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties. It also exhibits significant anti-tumor activity, suppressing tumor growth in vitro and in vivo. The current body of research on Britanin includes thirty papers predominantly related to neoplasms, the majority of which are gastrointestinal tumors that have not been summarized before. To drive academic debate, the present paper reviews the available research on Britanin in gastrointestinal tumors. It also outlines novel research directions using data not directly concerned with the digestive system, but which could be adopted in future gastrointestinal research. Britanin was found to counteract liver, colorectal, pancreatic, and gastric tumors, by regulating proliferation, apoptosis, autophagy, immune response, migration, and angiogenesis. As confirmed in pancreatic, gastric, and liver cancer, its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation, as well as Bcl-2-associated X protein upregulation. Moreover, it has been found to induce the Akt kinase and Forkhead box O1 axis, activate the AMP-activated protein kinase pathway, elevate interleukin-2 and peroxisome proliferator-activated receptor-γ levels, reduce interleukin-10, as well as downregulate matrix metalloproteinase-9, Twist family bHLH transcription factor 1, and cyclooxygenase-2. It also inhibits Myc-HIF1α interaction and programmed death ligand 1 transcription by interrupting the Ras/ RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling. Future research should aim to unravel the link between Britanin and acetylcholinesterase, mast cells, osteolysis, and ischemia, as compelling data have been provided by studies outside the gastrointestinal context. Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells, while still being effective against the latter, further in-depth studies with the use of animal models are merited. The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent, which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Antimicrobial and antibiofilm activity of specialized metabolites isolated from Centaurea hyalolepis.

The discovery of plant-derived compounds that are able to combat antibiotic-resistant pathogens is an urgent demand. Over years, Centaurea hyalolepis attracted considerable attention because of its beneficial medical properties. Phytochemical analyses revealed that Centaurea plant species contain several metabolites, such as sesquiterpene lactones (STLs), essential oils, flavonoids, alkaloids, and lignans.The organic extract of C. hyalolepis plant, collected in Palestine, showed significant antimicrobial properties towards a panel of Gram-negative and Gram-positive bacterial strains when the Minimal Inhibitory Concentration (MIC) values were evaluated by broth microdilution assays. A bio-guided fractionation of the active extract via multiple steps of column and thin layer chromatography allowed us to obtain three main compounds. The isolated metabolites were identified as the STLs cnicin, 11ß,13-dihydrosalonitenolide and salonitenolide by spectroscopic and spectrometric analyses. Cnicin conferred the strongest antimicrobial activity among the identified compounds. Moreover, the evaluation of its antibiofilm activity by biomass assays through crystal violet staining revealed almost 30% inhibition of biofilm formation in the case of A. baumannii ATCC 17878 strain. Furthermore, the quantification of carbohydrates and proteins present in the extracellular polymeric substance (EPS) revealed the ability of cnicin to significantly perturb biofilm structure. Based on these promising results, further investigations might open interesting perspectives to its applicability in biomedical field to counteract multidrug resistant infections.

Natural products as potential drug treatments for acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), which was once considered one of the deadliest types of leukemia, has become a curable malignancy since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as clinical treatments. ATO, which has become the first-line therapeutic agent for APL, is derived from the natural mineral product arsenic, exemplifying an important role of natural products in the treatment of APL. Many other natural products, ranging from small-molecule compounds to herbal extracts, have also demonstrated great potential for the treatment and adjuvant therapy of APL. In this review, we summarize the natural products and representative components that have demonstrated biological activity for the treatment of APL. We also discuss future directions in better exploring their medicinal value, which may provide a reference for subsequent new drug development and combination therapy programs.

Phosphine-Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin.

A general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of the zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly high efficiency of the phosphine-catalyzed Michael additions to this sesquiterpene lactone. Using n-Bu3P as the catalyst, pyrazole, phthalimide, 2-oxazolidinone, 4-quinazolinone, uracil, thymine, cytosine, and adenine adducts of arglabin were obtained. The n-Bu3P-catalyzed reaction of arglabin with active methylene compounds resulted in the predominant formation of bisadducts bearing a new quaternary carbon center. All synthesized Michael adducts and previously obtained phosphorylated arglabin derivatives were evaluated in vitro against eleven cancer and two normal cell lines, and the results were compared to those of natural arglabin and its dimethylamino hydrochloride salt currently used as anticancer drugs. 2-Oxazolidinone, uracil, diethyl malonate, dibenzyl phosphonate, and diethyl cyanomethylphosphonate derivatives of arglabin exhibited more potent antiproliferative activity towards several cancer cell lines and lower cytotoxicity towards normal cell lines in comparison to the reference compounds, indicating the feasibility of the developed methodology for the design of novel anticancer drugs with better therapeutic potential.

Green nanotech paradigm for enhancing sesquiterpene lactone therapeutics in cancer.

In the field of cancer therapy, sesquiterpene lactones (SLs) derived from diverse Dicoma species demonstrate noteworthy bioactivity. However, the translation of their full therapeutic potential into clinical applications encounters significant challenges, primarily related to solubility, bioavailability, and precise drug targeting. Despite these obstacles, our comprehensive review introduces an innovative paradigm shift that integrates the inherent therapeutic properties of SLs with the principles of green nanotechnology. To overcome issues of solubility, bioavailability, and targeted drug delivery, eco-friendly strategies are proposed for synthesizing nanocarriers. Green nanotechnology has emerged as a focal point in addressing environmental and health concerns linked to conventional treatments. This progressive approach of green nanotechnology holds promise for the development of safe and sustainable nanomaterials, particularly in the field of drug delivery. This groundbreaking methodology signifies a pioneering advancement in the creation of novel and effective anticancer therapeutics. It holds substantial potential for transforming cancer treatment and advancing the landscape of natural product research.

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.

Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis. Sesquiterpene lactones are one of the large and diverse groups of planet-derived phytochemicals that can be used as sources for a variety of drugs. Some sesquiterpene lactones possess many biological activities such as anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic. This review article briefly overviews the intrinsic and extrinsic pathways of apoptosis and the interactions between the modulators of both pathways. Also, the present review summarizes the potential effects of sesquiterpene lactones on different modulators of the intrinsic and extrinsic pathways of apoptosis in a variety of cancer cell lines and animal models. The main purpose of the present review is to give a clear picture of the current knowledge about the pro-apoptotic effects of sesquiterpene lactones on various cancers to provide future direction in cancer therapeutics.

Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora.

Four new sesquiterpene lactones (SLs) (1-4), along with a biosynthetically related SL (5), have been isolated from the leaves of Magnolia grandiflora. Magrandate A (1) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3, representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single-crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3-5 showed a significant inhibitory effect on nitric oxide production, with IC50 values ranging from 0.79 to 4.73 µmol·L-1. Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC50 values between 3.09 and 11.23 µmol·L-1.

Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties.

Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including Acmella bellidioides, Campuloclinium macrocephalum, Grindelia pulchella, Grindelia chiloensis, Helenium radiatum, and Viguiera tuberosa, along with pure phytochemicals isolated from Asteraceae: mikanolide (1), eupatoriopicrin (2), eupahakonenin B (3), minimolide (4), estafietin (5), 2-oxo-8-deoxyligustrin (6), santhemoidin C (7), euparin (8), jaceidin (9), nepetin (10), jaceosidin (11), eryodictiol (12), eupatorin (13), and 5-demethylsinensetin (14). Results showed that the dichloromethane extracts of C. macrocephalum and H. radiatum and the methanolic extracts prepared from C. macrocephalum and G. pulchella were highly active and selective against DENV-2, affording EC50 values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds 6, 7, and 8 stand out as the most active (EC50 = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.

Hirsutinolide- and Cadinanolide-type Sesquiterpene Lactones from Lessingianthus rubricaulis (Vernonieae, Asteraceae).

Sesquiterpene lactones are an important class of secondary metabolites frequently isolated from Lessingianthus genus that present a variety of biological properties, such as antimalarial, anti-inflammatory, antileishmanial, antitrypanosomal and anticancer. The limited phytochemical studies and the importance of this class of compounds isolated from Lessingianthus led us to study this genus. In this work, we focused on the phytochemical investigation and dereplication based on UHPLC-HRMS/MS and molecular networking of L. rubricaulis. Chemical investigation resulted in the isolation of several hirsutinolide-type sesquiterpene lactones including a new hirsutinolide derivative, 8,10α-hydroxy-1,13-bis-O-methylhirsutinolide, besides a cadinanolide and flavonoids. The dereplication study resulted in the identification of three known flavonoids, six known hirsutinolides and two known cadinanolides. Moreover, a fragmentation pathway for cadinanolide-type sesquiterpene lactones was proposed. These results contribute to chemotaxonomic studies and demonstrates the potential of Lessingianthus genus.

Microwave-assisted extraction optimization of sesquiterpene lactones from Inula helenium roots: A sustainable approach to reduce energy consumption and carbon footprint.

Inula helenium roots are consumed as natural flavor components and raw or cooked as food, and their extracts are rich in sesquiterpene lactones such as alantolactone (AL) and isoalantolactone (IAL), which have recently attracted great attention due to their pharmacological properties. The industrial utilization of these compounds requires the development of green, efficient, cost-effective, and sustainable extraction protocols. Therefore, this study focused on the optimization of microwave-assisted extraction (MAE) process variables using Face-Centered Central Composite Design (FC-CCD). Then, maceration was applied as a conventional technique, and these techniques were compared in terms of extraction efficiency, morphological changes, antimicrobial activities, carbon emissions, and energy consumption. As a result, optimal MAE conditions, i.e., EtOH: water ratio (X 1) = 100:0, liquid/sample ratio (X 2) = 30:1 mL/g, microwave power (X 3) = 300 W, and irradiation time (X 4) = 5 min, were obtained with AL and IAL yields of 54.99 ± 0.11 (mg/g) and 48.40 ± 0.19 (mg/g), respectively. The extract obtained by MAE had similar or better activity than positive controls in most cases and formed the largest inhibition zones against E. coli (29.5 ± 0.71 mm) and A. niger (34.75 ± 1.06 mm). Morphological changes of I. helenium roots after extraction were observed by scanning electron microscopy. Additionally, MAE was 43.4 times faster than maceration, resulting in 228.6 times less energy consumption and carbon emissions. Based on these findings, it is recommended to use MAE as an industrial green technique for the extraction of sesquiterpene lactones with potential applications in nutraceuticals and food products in terms of sustainable economy and environmental protection.

Hysterolides A-I, dimeric or monomeric sesquiterpene lactones from Parthenium hysterophorus L.

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4-9), along with 13 known analogues (10-22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52-6.32 µM. Furthermore, the preliminary structure-activity relationship was also established.

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

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.