Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/20/2007
Publication Date: 12/1/2007
Citation: Cantrell, C.L., Duke, S.O., Fronczek, F.R., Osbrink, W.L., Mamonov, L.K., Vassilyev, J.I., Wedge, D.E., Dayan, F.E. 2007. Phytotoxic Eremophilanes from Ligularia macrophylla. Journal of Agricultural and Food Chemistry. v. 55:10656-10663. Interpretive Summary: Natural products are a source of compounds that might be used directly as pesticides or as the template for new synthetic pesticides. In this paper we systematically examine Ligularia macrophylla, a high altitude species native to the Republic of Kazakhstan for insecticidal, fungicidal, and herbicidal activity. This species and other species of this genus have been studied from a phytochemical standpoint (e.g., there are quite a few papers that can be cited); however, evaluation of the biological activities of compounds from this species is sparse. We are aware of few studies for pesticide discovery from this genus except for two studies that examined Ligularia species for insecticidal activity and one patent on herbicidal properties of L. stenocephala compounds. Of particular interest from the present study was the herbicidal activity of the eremophilanes. The most promising compound as a potential pesticide lead was 6B-angeloyloxy-10B-hydroxyfuranoeremophilane. Its activity on L. paucicostata was higher than that of many commercial herbicides. It deserves further study for structure optimization and to determine is mode of action.
Technical Abstract: Systematic bioassay-guided fractionation of the methylene chloride roots extract of Ligularia macrophylla was performed to identify both phytotoxic and antifungal compounds. Four phytotoxic eremophilanes [furanoeremophilan-14B,6a-olide, 6B-angeloyloxy-10B-hydroxyfuranoeremophilane, eremophil-7(11)-ene-12,8a;14B,6a-diolide, and 3a-angeloyloxybakkenolide A] and two antifungal fatty acids (linoleic acid and a-linolenic acid) were isolated. All four eremophilanes substantially inhibited growth of the monocot Agrostis stolonifera (bentgrass) while demonstrating little activity against the dicot Lactuca sativa (lettuce) at 1000 uM. In a dose-response screening of all compounds for growth inhibitory activity against Lemna paucicostata, 6B-angeloyloxy-10B-hydroxyfuranoeremophilane was the most active with an I50 of 2.94 ± 0.16 uM. This compound also caused the greatest reduction of photosynthetic electron flow; however, its mode of action remains to be determined. The X-ray crystal structure determination of 6B-angeloyloxy-10B-hydroxyfuranoeremophilane is reported here for the first time. Evaluation of isolated compounds for activity against the Formosan subterranean termite, Coptotermes formosanus, is also reported. At a concentration of 0.5%, 6B-angeloyloxy-10B-hydroxyfuranoeremophilane significantly reduced the consumption of filter paper by C. formosanus.