Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae) / Acción insecticida de análogos sintéticos de girgensohnina y de aceites esenciales sobre Rhodnius prolixus (Hemiptera: Reduviidae)

ABSTRACT Introduction: The alkaloid girgensohnine has been used as a natural model in the synthesis of new alkaloid-like alpha-aminonitriles with insecticidal effect against disease vectors. Objective: To evaluate the biocide activity of girgensohnine analogues and essential oils of Cymbopogon flexuosus, Citrus sinensis and Eucalyptus citriodora in stage I and stage V Rhodnius prolixus nymphs. Materials and methods: We used a topical application model in tergites and sternites, as well as exposure to treated surfaces with different exploratory doses of each of the molecules and essential oils to determine the lethal doses (LD50 and LD95). Results: Analogue 3 showed the highest insecticidal activity with 83.3±16.7% of mortality when applied on tergites, 38.9±4.8% on sternites and 16.7±0% on treated surfaces in stage I nymphs at 72 hours (h) and 500 mg.L-1. In stage V nymphs, the compounds induced mortality only in sternums (11.1±9.6% for analogue 6 and 5.5±4.7% for analogues 3 and 7 at 72 h and 1500 mg.L-1). The lethal doses for molecule 3 on tergites in stage I nymphs were LD50 225.60 mg.L-1 and LD95 955.90 mg.L-1. The insecticidal effect of essential oils was observed only in stage I nymphs, with 11.1±4.8% for C. flexuosus when applied in sternites, while using exposure to surfaces treated it was 5.6±4.8% for C. sinensis applied on tergites and 8.3±0% on sternites at 72 h and 1000 mg.L-1. Conclusion: Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

RESUMEN Introducción. El alcaloide natural girgensohnina se ha usado como modelo en la síntesis de nuevos análogos de alcaloidales alfa-aminonitrílicos con efecto insecticida en vectores de enfermedades. Objetivo. Evaluar la actividad biocida de análogos de girgensohnina y de aceites esenciales de las plantas Cymbopogon flexuosus, Citrus sinensis y Eucalyptus citriodora en ninfas de estadios I y V de Rhodnius prolixus. Materiales y métodos. Se empleó la aplicación tópica en terguitos, esternitos y superficies tratadas con diferentes dosis exploratorias de cada una de las moléculas y aceites esenciales para determinar las dosis letales (LD50 y LD95). Resultados. El análogo 3 tuvo la mayor actividad insecticida, con una mortalidad de 83,3±16,7% en los terguitos, de 38,9±4,8 % en los esternitos y de 16,7±0 % a las 72 horas en ninfas de estadioI expuestas a superficies tratadas y 500 mg.L-1. En las ninfas de estadio V solo se presentó mortalidad en los esternitos (11,1±9,6 % con el análogo 6 y 5,5±4,7 % con los análogos 3 y 7 a las 72 h y 1.500 mg.L-1). Las dosis letales para la molécula 3 en los terguitos de ninfas de estadio I fueron las siguientes: DL50, 225,60 mg.L-1 y DL95, 955,90 mg.L-1. En cuanto a los aceites esenciales, el efecto insecticida solo se presentó con C. flexuosus (11,1±4,8%) en los esternitos de ninfas de estadio I expuestas a superficies tratadas; con C. sinensis (5,6±4,8%) en los terguitos y en los esternitos (8,3±0%) a las 72 horas y 1.000 mg.L-1. Conclusión. Los análogos sintéticos del alcaloide girgensohnina y los aceites esenciales de C. flexuosus y C. sinensis exhibieron actividad insecticida en R. prolixus. El análogo 3 exhibió la mayor actividad insecticida de todas las moléculas evaluadas bajo las condiciones de laboratorio.

Focus on the synthesis and reactions of some new pyridine carbonitrile derivatives as antimicrobial and antioxidant agents

3-[4-CHLOROPHENYL]-1-[2, 4-dichlorophenyl]-propen-1-one [1] was prepared and reacted with active methylene compound, ethyl cyanoacetate in the presence of ammonium acetate 10 give the corresponding pyridine carbonitrile [2]. The behavior of compound 2 towards phosphorous pentasulfide, phosphorous oxychloride and some acyclic-sugars has been investigated and afforded compounds 3, 4 and 5a-d, respectively. The thioxo-pyridine carbonitrile [3] reacted with different halo compounds namely: methyl iodide, ethyl chloroacetate, some acyclic sugars to afford 6, 7 and 8a-c, respectively. Treatment of compound 3 with acrylonitrile afforded compound 9. Reaction of the thiosulfanyl 6 with hydrazine hydrate gave the hydrazine derivative 10 while reaction of 7 with the same reagents gave the acid hydrazide 11. Also, compound 4 reacted with different nucleophiles to afford compounds 10, 12-14. Condensation of compound 10 with ethyl acetoacetate, acetyl acetone, acetic anhydride, p-chlorobenzaldehyde afforded compounds 15-18, respectively. Moreover, compound 10 reacted with carbon disulfide to afford compound 19. Finally, condensation of compound 10 with aldehydo-sugar namely: D-glucose gave the corresponding acyclic nucleoside 20. Furthermore, biological evaluation of some prepared compounds has been assessed and some of them revealed promising antimicrobial and antioxidant activity

FK778, A Synthetic Malononitrilamide

FK778 is a synthetic malononitrilamide (MNA) that has been demonstrated to have both both immunosuppressive and anti-proliferative activities. The MNAs inhibit both T-cell and B-cell function by blocking de novo pyrimidine synthesis, through blockade of the pivotal mitochondrial enzyme dihyroorotic acid dehydrogenase (DHODH), and the inhibition of tyrosine kinase activity. FK778 has been demonstrated to prevent acute allograft rejection in multiple experimental transplant models in rodents, dogs and primates and to be effective in the rat model of chronic renal allograft rejection. In addition, FK778 has been shown to prevent vascular remodeling after mechanical intimal injury via a mechanism which may be related to tyrosine kinase inhibitory activity in vascular smooth muscle cells. Another intriguing activity of the MNA family is the ability to block replication of members of the Herpes virus family with in vitro evidence that of efficacy against cytomegalovirus (CMV) and polyoma virus, important pathogens in the transplant recipient. FK778 is currently being explored in a number of trials in solid organ transplant recipients.