RESUMEN
To develop the novel ryanodine receptors (RyRs) insecticides, encouraged by our previous research work, a series of novel N-phenylpyrazole derivatives containing a polysubstituted phenyl ring scaffold were designed and synthesized. The bioassays results indicated that some title compounds exhibited excellent insecticidal activity. For oriental armyworm (Mythimna separata), compounds 7f, 7g, 7i and 7o at 0.5 mg L-1 displayed 100% larvicidal activity, and even at 0.1 mg L-1, 7o was 30% larvicidal activity, comparable to chlorantraniliprole (30%) and better than cyantraniliprole (10%). Compounds 7f and 7o had the median lethal concentrations (LC50) of 8.83 × 10-2 and 7.12 × 10-2 mg L-1, respectively, close to chlorantraniliprole (6.79 × 10-2 mg L-1). Additionally, for diamondback moth (Plutella xylostella), the larvicidal activity of compounds 7f and 7i were 90% and 70% at 0.01 mg L-1, respectively, better than chlorantraniliprole (50%) and cyantraniliprole (40%). More impressively, the LC50 value of 7f was 4.2 × 10-3 mg L-1, slightly lower than that of chlorantraniliprole (5.0 × 10-3 mg L-1). The molecular docking between compound 7f and RyRs of diamondback moth validated our molecular designation. Furthermore, the calcium imaging experiment explored the influence of compound 7o on the calcium homeostasis in the central neurons of the third larvae of oriental armyworm. The results of this study indicated that 7o is a potent novel lead targeting at RyRs.
Asunto(s)
Agonistas de los Canales de Calcio/química , Pirazoles/química , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Animales , Sitios de Unión , Agonistas de los Canales de Calcio/metabolismo , Agonistas de los Canales de Calcio/farmacología , Señalización del Calcio/efectos de los fármacos , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Insecticidas/química , Insecticidas/metabolismo , Insecticidas/farmacología , Larva/efectos de los fármacos , Simulación del Acoplamiento Molecular , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Pirazoles/metabolismo , Pirazoles/farmacología , Canal Liberador de Calcio Receptor de Rianodina/química , Relación Estructura-ActividadRESUMEN
Novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues were efficiently synthesized and their biological activities were evaluated. 2alpha-Methyl-1alpha,25-dihydroxyvitamin D3 (2), whose unique biological activities were previously reported, was modified to 2alpha-alkyl (ethyl and propyl) and 2alpha-hydroxyalkyl (hydroxymethyl, hydroxyethyl, and hydroxypropyl) analogues 3-7 by elongation of the alkyl chain and/or introduction of a terminal hydroxyl group. 2alpha-Hydroxypropyl-1alpha,25-dihydroxyvitamin D3 (7) exhibited an exceptionally potent calcium-regulating effect and a unique activity profile.