Toxicity of thiophenes from Echinops transiliensis (Asteraceae) against Aedes aegypti (Diptera: Culicidae) larvae.

Structureactivity relationships of nine thiophenes, 2,2': 5',2″-terthiophene (1), 2-chloro-4-[5-(penta-1,3-diyn-1-yl)thiophen-2-yl]but-3-yn-1-yl acetate (2), 4-(2,2'-bithiophen-5-yl)but-3-yne-1,2-diyl diacetate (3), 4-[5-(penta-1,3-diyn-1-yl)thiophen-2-yl]but-3-yne-1,2-diyl diacetate (4), 4-(2,2'-bithiophen-5-yl)-2-hydroxybut-3-yn-1-yl acetate (5), 2-hydroxy-4-[5-(penta-1,3-diyn-1-yl)thiophen-2-yl]but-3-yn-1-yl acetate (6), 1-hydroxy-4-[5-(penta-1,3-diyn-1-yl)thiophen-2-yl]but-3-yn-2-yl acetate (7), 4-(2,2'-bithiophen-5-yl)but-3-yne-1,2-diol (8), and 4-[5-(penta-1,3-diyn-1-yl)thiophen-2-yl]but-3-yne-1,2-diol (9), isolated from the roots of Echinops transiliensis, were studied as larvicides against Aedes aegypti. Structural differences among compounds 3, 5, and 8 consisted in differing AcO and OH groups attached to C(3″) and C(4″), and resulted in variations in efficacy. Terthiophene 1 showed the highest activity (LC50 , 0.16 µg/ml) among compounds 1-9, followed by bithiophene compounds 3 (LC50 , 4.22 µg/ml), 5 (LC50 , 7.45 µg/ml), and 8 (LC50 , 9.89 µg/ml), and monothiophene compounds 9 (LC50 , 12.45 µg/ml), 2 (LC50 , 14.71 µg/ml), 4 (LC50 , 17.95 µg/ml), 6 (LC50 , 18.55 µg/ml), and 7 (LC50 , 19.97 µg/ml). These data indicated that A. aegypti larvicidal activities of thiophenes increase with increasing number of thiophene rings, and the most important active site in the structure of thiophenes could be the tetrahydro-thiophene moiety. In bithiophenes, 3, 5, and 8, A. aegypti larvicidal activity increased with increasing number of AcO groups attached to C(3″) or C(4″), indicating that AcO groups may play an important role in the larvicidal activity.

Phytotoxic furanocoumarins from the shoots of Semenovia transiliensis.

Discovery of novel, natural herbicides has become important to manage increasing weed resistance to synthetic herbicides and environmental issues. The systematic bioassay-guided fractionation and purification of the methylene chloride/methanol extract of the shoots of Semenovia transiliensis led to the isolation of several phytotoxic compounds. Lactuca sativa L. (lettuce, a dicot) and Agrostis stolonifera L. (bentgrass, a monocot) bioassays were used to identify and isolate the phytotoxic fractions. A number of furanocoumarin compounds isolated from S. transiliensis shoots were phytotoxic to both test species. These included psoralen, isopsoralen, heratomin, isopentenyloxyisobergapten, imperatorin, bergapten, xanthotoxin, heraclenin, and heraclenol. All the active secondary metabolites isolated from the shoots of S. transiliensis were furanocoumarins. Identification of these was accomplished using mass spectrometry and 1- and 2-dimensional NMR techniques. Phytotoxic activity o f isolated compounds w a s evaluated in a dose-response manner from 0.3 to 1000 microM. Ingeneral, all of the compounds were more active on A. stolonifera than L. sativa. Bergaptin and xanthotoxin were the most active of the compounds, with moderate activity at 100 microM. Imperatorin and xanthotoxin inhibited growth of Lemna paucicostata Hegelm. by 50% at 29 and 60 microM, respectively. Our results show that S. transiliensis is rich in furanocoumarins, which are probably involved in various aspects of the chemical ecology of the species. Unfortunately, the general cytotoxicity of furanocoumarins makes them an unlikely candidate for pesticide discovery.

Isolation and identification of Flavobacterium columnare and Streptococcus iniae antibacterial compounds from the terrestrial plant Atraphaxis laetevirens.

Columnaris disease, enteric septicemia of catfish, and streptococcosis are common bacterial diseases of certain freshwater fish and are caused by Flavobacterium columnare , Edwardsiella ictaluri , and Streptococcus iniae , respectively. During the process of evaluating several species of plants to isolate and identify compounds with toxicity against these bacteria, a promising extract from the aerial parts of the terrestrial plant Atraphaxis laetevirens (Ledeb.) Jaub. et Spach (Polygonaceae Juss.) was selected for bioassay-guided fractionation using a rapid microplate bioassay. The active dichloromethane extract was subjected to liquid-liquid partitioning, and active fractions were further separated by normal-phase column chromatography and normal-phase high-performance liquid chromatography (HPLC). Nepodin (3) and emodin (4) were isolated from two fractions with strong toxicities against S. iniae . A chloroform fraction was further separated by normal-phase column chromatography to yield two active fractions against F. columnare , and these fractions contained chrysophanol (1), physcion (2), and nepodin (3). Compound 1 had strong activity, and compound 3 had moderate activity against F. columnare , while compounds 2 and 4 were not toxic at the concentrations tested.

Echinopsacetylenes A and B, new thiophenes from Echinops transiliensis.

Two new polyacetylene thiophenes, echinopsacetylenes A and B (1 and 2), were isolated from the roots of Echinops transiliensis. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses and chemical transformations. Echinopsacetylenes A (1) is the first natural product possessing an α-terthienyl moiety covalently linked with another thiophene moiety. Echinopsacetylenes B (2) is the first natural thiophene conjugated with a fatty acid moiety. Echinopsacetylene A (1) showed toxicity against the Formosoan subterranean termite (Coptotermes formosanus).

Phytotoxic Eremophilanes from Ligularia macrophylla.

Systematic bioassay-guided fractionation of the methylene chloride extract of the roots from Ligularia macrophylla was performed to identify both phytotoxic and antifungal compounds. Four phytotoxic eremophilanes (furanoeremophilan-14beta,6alpha-olide, 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane, eremophil-7(11)-ene-12,8alpha;14beta,6alpha-diolide, and 3alpha-angeloyloxybakkenolide A) and two antifungal fatty acids (linoleic acid and alpha-linolenic acid) were isolated. The X-ray crystal structure determination of 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane is reported here for the first time. All four eremophilanes substantially inhibited growth of the monocot Agrostis stolonifera (bentgrass) while demonstrating little activity against the dicot Lactuca sativa (lettuce) at 1000 microM. In a dose-response screening of all compounds for growth inhibitory activity against Lemna paucicostata, 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane was the most active with an IC50 of 2.94+/-0.16 microM. This compound also caused the greatest reduction of photosynthetic electron flow; however, its mode of action remains to be determined. Evaluation of isolated compounds for activity against the Formosan subterranean termite, Coptotermes formosanus, is also reported. At a concentration of 0.5% (wt/wt), 6beta-angeloyloxy-10beta-hydroxyfuranoeremophilane significantly reduced the consumption of filter paper by C. formosanus.

Antifeedant and toxicity effects of thiophenes from four Echinops species against the Formosan subterranean termite, Coptotermes formosanus.

Over 220 crude extracts from repositories generated from plants native to Greece and Kazakhstan were evaluated for termiticidal activity against the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae). Emerging from this screening effort were bioactive extracts from two Greek species (Echinops ritro L. and Echinops spinosissimus Turra subsp. spinosissimus) and extracts from two Kazakhstan species (Echinops albicaulis Kar. & Kir. and Echinops transiliensis Golosh.). Fractionation and isolation of constituents from the most active extracts from each of the four species has been completed, resulting in the isolation of eight thiophenes possessing varying degrees of termiticidal activity. 2,2':5',2"-Terthiophene and 5'-(3-buten-1-ynyl)-2,2'-bithiophene demonstrated 100% mortality against C. formosanus within 9 days at 1 and 2 wt% concentrations respectively. In addition, all but two of the eight compounds tested were significantly different from the solvent controls in the filter paper consumption bioassay.