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

Fungal 10-membered lactones (TMLs), such as stagonolide A, herbarumin I, pinolidoxin, and putaminoxin, are promising candidates for the development of nature-derived herbicides. The aim of this study was to analyze the structure-activity relationships (SAR) of C-9-methyl-substituted TMLs with a multitarget bioassay approach to reveal compounds with useful (phytotoxic, entomotoxic, antimicrobial) or undesirable (cytotoxic) bioactivities. A new TML, stagonolide L (1), along with five known compounds (stagonolides D (2) and E (3), curvulides A (4) and B1/B2 (5a,b), and pyrenolide C (6)), were purified from cultures of the phytopathogenic fungus Stagonospora cirsii, and five semisynthetic derivatives of 3 and 4 (7-11) were obtained. The absolute configuration of 4 was revised to 2Z, 4S, 5S, 6R, and 9R. The identity of 5a,b and stagonolide H is discussed. The phytotoxicity of compound 4, the entomotoxicity of 5a,b, and nonselective toxicity of compound 6 are demonstrated. The latter confirms the hypothesis that the α,ß-unsaturated carbonyl group is associated with the high general toxicity of TML, regardless of its position in the ring and other substituents. The epoxide in compound 4 is important for phytotoxicity. The revealed SAR patterns will be useful for further rational design of TML-based herbicides including curvulide A analogs with a 4,5-epoxy group.

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid.

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.

Fumigant effect of essential oils on mortality and fertility of thrips Frankliniella occidentalis Perg.

The western flower thrips (Frankliniella occidentalis Perg.) is one of the most economically important insect pests of greenhouse plants. Plant protection against this pest is based predominantly on synthetic insecticides; however, this form of protection poses problems in terms of thrip resistance to the active substances, along with health risks associated with insecticide residues on the treated plants. Therefore, new active substances need to be sought. Essential oils could be a new, appropriate, and safe alternative for greenhouse culture protection. As greenhouses are enclosed areas, fumigation application of EOs is possible. This paper presents acute toxicity results for 15 commercial EOs applied by fumigation, as well as the effect of sublethal concentrations on fertility of F. occidentalis females. The most efficient EOs were obtained from Mentha pulegium and Thymus mastichina, with LC50(90) estimated as 3.1(3.8) and 3.6 (4.6) mg L-1 air, respectively. As found for the very first time, sublethal concentrations of EOs could result in a significant reduction in the fertility of surviving T. occidentalis females. Among the tested EOs, the EO from Nepeta cataria provided the highest inhibition of fertility, with EC50(90) estimated as 0.18 (0.36) mg L-1 air. Chemical composition of the most efficient EOs and possible applications of the results in practice are discussed. In conclusion, in light of the newly determined facts, EOs can be recommended as active substances for botanical insecticides to be applied against Thysanopteran pests by fumigation.