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 mg/ml) among compounds 1-9, followed by bithiophene compounds 3 (LC50, 4.22 mu g/ml), 5 (LC50, 7.45 mu g/ml), and 8 (LC50, 9.89 mu g/ml), and monothiophene compounds 9 (LC50, 12.45 mu g/ml), 2 (LC50, 14.71 mu g/ml), 4 (LC50, 17.95 mu g/ml), 6 (LC50, 18.55 mu g/ml), and 7 (LC50, 19.97 mu g/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.