Weeds are a permanent component of anthropogenic ecosystems. They require strict control to avoid the accumulation of their long-lasting seeds in the soil. With high crop infestation, many elements of crop production technologies (fertilization, productive varieties, growth stimulators, etc.) turn out to be practically meaningless due to high yield losses. Intensive use of chemical herbicides (CHs) has led to undesirable consequences: contamination of soil and wastewater, accumulation of their residues in the crop, and the emergence of CH-resistant populations of weeds. In this regard, the development of environmentally friendly CHs with new mechanisms of action is relevant. The natural phytotoxins of plant or microbial origin may be explored directly in herbicidal formulations (biorational CHs) or indirectly as scaffolds for nature-derived CHs. This review considers (1) the main current trends in the development of CHs that may be important for the enhancement of biorational herbicides; (2) the advances in the development and practical application of natural compounds for weed control; (3) the use of phytotoxins as prototypes of synthetic herbicides. Some modern approaches, such as computational methods of virtual screening and design of herbicidal molecules, development of modern formulations, and determination of molecular targets, are stressed as crucial to make the exploration of natural compounds more effective.

Biorational insecticides (for instance, avermectins, spinosins, azadirachtin, and afidopyropen) of natural origin are increasingly being used in agriculture. The review considers the chemical ecology approach for the search for new compounds with insecticidal properties (entomotoxic, antifeedant, and hormonal) produced by fungi of various ecological groups (entomopathogens, soil saprotrophs, endophytes, phytopathogens, and mushrooms). The literature survey revealed that insecticidal metabolites of entomopathogenic fungi have not been sufficiently studied, and most of the well-characterized compounds show moderate insecticidal activity. The greatest number of substances with insecticidal properties was found to be produced by soil fungi, mainly from the genera Aspergillus and Penicillium. Metabolites with insecticidal and antifeedant properties were also found in endophytic and phytopathogenic fungi. It was noted that insect pests of stored products are mostly low sensitive to mycotoxins. Mushrooms were found to be promising producers of antifeedant compounds as well as insecticidal proteins. The expansion of the number of substances with insecticidal properties detected in prospective fungal species is possible by mining fungal genomes for secondary metabolite gene clusters and secreted proteins with their subsequent activation by various methods. The efficacy of these studies can be increased with high-throughput techniques of extraction of fungal metabolites and their analysis by various methods of chromatography and mass spectrometry.

The fungus, Alternaria sonchi is considered to be a potential agent for the biocontrol of perennial sowthistle (Sonchus arvensis). A new chlorinated xanthone, methyl 8-hydroxy-3-methyl-4-chloro-9-oxo-9H-xanthene-1-carboxylate (1) and a new benzophenone derivative, 5-chloromoniliphenone (2), were isolated together with eleven structurally related compounds (3–13) from the solid culture of the fungus, which is used for the production of bioherbicidal inoculum of A. sonchi. Their structures were determined by spectroscopic (mostly by NMR and MS) methods. Alternethanoxins A and B, which were reported in A. sonchi earlier, were re-identified as moniliphenone and pinselin, respectively. The isolated compounds were tested for phytotoxic, antimicrobial, insecticidal, cytotoxic and esterase-inhibition activities. They did not demonstrate high phytotoxicity (lesions up to 2.5 mm in diameter/length at a concentration of 2 mg/mL) when tested on leaf disks/segments of perennial sowthistle (Sonchus arvensis) and couch grass (Elytrigia repens). They did not possess acute toxicity to Paramecium caudatum, and showed moderate to low cytotoxicity (IC₅₀ > 25 µg/mL) for U937 and K562 tumor cell lines. However, chloromonilicin and methyl 3,8-dihydroxy-6-methyl-4-chloro-9-oxo-9H-xanthene-1-carboxylate (4) were shown to have antimicrobial properties with MIC 0.5–5 µg/disc. Compound 4 and chloromonilinic acid B were found to have contact insecticidal activity to wheat aphid (Schizaphis graminum) at 1 mg/mL. Compounds 2 and methyl 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate displayed selective carboxylesterase inhibition activity at concentration of 100 µg/mL. Therefore, the waste solid substrate for production of A. sonchi spores can be re-utilized for the isolation of a number of valuable natural products.

More than 300 metabolites of fungi of the genera Alternaria have been reported in the last few decades; some of them display phytotoxic, antibiotic, antifungal, and antiprotozoal activity. This review synthesizes the current information on the structure, biological activity, and possible application of Alternaria metabolites in plant protection, pharmacology, and chemotaxonomy. Some Alternaria fungi are suggested as mycoherbicides. The toxicology of application of the Alternaria fungi as mycoherbicides is discussed.

Phoma-like fungi are known as producers of diverse spectrum of secondary metabolites, including phytotoxins. Our bioassays had shown that extracts of Paraphoma sp. VIZR 1.46, a pathogen of Cirsium arvense, are phytotoxic. In this study, two phytotoxically active metabolites were isolated from Paraphoma sp. VIZR 1.46 liquid and solid cultures and identified as curvulin and phaeosphaeride A, respectively. The latter is reported also for the first time as a fungal phytotoxic product with potential herbicidal activity. Both metabolites were assayed for phytotoxic, antimicrobial and zootoxic activities. Curvulin and phaeosphaeride A were tested on weedy and agrarian plants, fungi, Gram-positive and Gram-negative bacteria, and on paramecia. Curvulin was shown to be weakly phytotoxic, while phaeosphaeride A caused severe necrotic lesions on all the tested plants. To evaluate phaeosphaeride A’s herbicidal efficacy, the phytotoxic activity of this compound in combination with five different adjuvants was studied. Hasten at 0.1% (v/v) was found to be the most potent and compatible adjuvant, and its combination with 0.5% (v/v) semi-purified extract of Paraphoma sp. VIZR 1.46 solid culture exhibited maximum damage to C. arvense plants. These findings may offer significant importance for further investigation of herbicidal potential of phaeosphaeride A and possibly in devising new herbicide of natural origin.

The study of fungal antibiotics in their competitive interactions with arthropods may lead to the development of novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained using various methods showed a wide range of biological activities, including entomotoxic properties. Analysis of their composition and bioactivity allowed us to reveal several known mycotoxins and unidentified compounds that may be involved in the entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with an LT₅₀ of 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited the growth of G. mellonella larvae and caused mortality of Acheta domesticus adults (LT₅₀ 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing 15% and 27% mortality at a concentration of 1 mg/mL, respectively. TeA was cytotoxic to the Sf9 cell line (IC₅₀ 25 µg/mL). Thus, model insects such as G. mellonella could be used for further toxicological characterization of TeA.