Abstract Background: Estrogens that are used as contraceptives or in replacement therapy are associated with an increase in the risk for developing thrombosis, mainly during the first year of treatment and in women with associated risk factors. Objective: To synthesize, characterize and identify the anticoagulant, antiplatelet aggregation and microvesicle-reducing effect of the new aminoestrogen Tyrame. Material and methods: CD1 strain mice were used, which had Tyrame (0, 1 and 2 mg/100 g) subcutaneously administered. At 24 h, a blood sample was obtained to determine whole-blood clotting time, microvesicles concentration and inhibitory effect on platelet aggregation. Results: Blood clotting time increased up to 1.5 times in comparison with the control. Platelet aggregation inhibition had different magnitude depending on the agonist agent employed, and was complete with collagen. Both effects had a dose-dependent relationship. The microvesicles decreased up to six times with respect to the control. Conclusions: Tyrame reduces platelet aggregation and microvesicle formation, which emphasizes its potential therapeutic utility as an estrogen free of thrombotic effects.

Resumen Antecedentes: Los estrógenos empleados como anticonceptivos o en la terapia de sustitución se asocian a un incremento en el riesgo de desarrollar trombosis, principalmente durante el primer año de tratamiento y en mujeres con factores de riesgo asociados. Objetivo: Sintetizar, caracterizar e identificar el efecto anticoagulante, antiagregante plaquetario y reductor de las microvesículas del nuevo aminoestrógeno tyrame. Material y métodos: Se emplearon ratones cepa CD1 a los que se les administró por vía subcutánea tyrame (0, 1 y 2 mg/100 g). A las 24 h se tomó una muestra de sangre para determinar el tiempo de coagulación en sangre total, la concentración de microvesículas y el efecto inhibidor de la agregación plaquetaria. Resultados: El tiempo de coagulación en sangre se incrementó hasta 1.5 veces con respecto al control. La inhibición de la agregación plaquetaria tuvo diferente magnitud dependiendo del agente agonista, siendo completa con colágena. Ambos efectos siguieron una relación dependiente de la dosis. Las microvesículas disminuyeron hasta seis veces con respecto al control. Conclusiones: el tyrame disminuye la agregación plaquetaria y la formación de microvesículas, lo que acentúa su posible utilidad terapéutica como un estrógeno sin efectos trombóticos.

Abstract: Sapium macrocarpum (Euphorbiaceae) is a tropical tree located mainly in the southern part of Mexico and in Central America, and it is used in the Mayan traditional medicine for the treatment of several skin diseases. The dichloromethane-MeOH extract of the aerial parts displayed cytotoxic activity against certain cancer cell lines. Lupeol (1), lupenone (2), sitostenone (3), β-sitosterol (4), stigmasterol (5), sitosteryl β-D-glucopyranoside (6) and the rare diterpene tonantzi tlolone A (7) were characterized from this extract. The structural analysis allowed the 1H NMR reassignments for H-12α and H-12β, and for H-13α and H-13β of tonantzitlolone A (7). The cytotoxic activity of compounds 1-3, 6 and 7 was evaluated against selected cancer cell lines. Compounds 3, 6 and 7 displayed clear activity against K562 (leukemia). This is the first report on the chemical constituents of S. macrocarpum, and points out that this species is an additional source of tonantzitlolone A. Compound 7 has only been reported previously from species of the Stillingia, Sebastiania and Sapium genera, which belong to the Hippomaninae subtribe of the family Euphorbiaceae.

Resumen: Sapium macrocarpum (familia Euphorbiaceae) es un árbol localizado en la parte central de México y en Sudamérica, el cual es usado en la medicina tradicional Maya para el tratamiento de diversas enfermedades de la piel. El extracto de diclorometano-metanol de las partes aéreas de esta especie mostró actividad inhibitoria de la proliferación de ciertas células cancerosas humanas. Lupeol (1), lupenona (2), sitostenona (3), β-sitosterol (4), estigmasterol (5), β-D-glucopiranósido de sitosterilo (6) y el diterpeno relativamente raro tonantzitlolona A (7) fueron caracterizados de este extracto. El análisis estructural de la tonantzitlolona A (7) permitió la reasignación de las señales de RMN 1H de H-12α y H-12β, y de H-13α y H-13β. La actividad citotóxica de los compuestos 1-3, 6 y 7 fue evaluada frente a las líneas celulares cancerosas selectas. Los compuestos 3, 6 y 7 mostraron actividad clara contra K562 (leucemia). Este es el primer reporte sobre los constituyentes químicos de S. macrocarpum, encontrando que esta especie constituye una fuente adicional de tonantzitlolona A. El compuesto 7 ha sido aislado de los géneros Stillingia, Sebastiania y Sapium, los cuales pertenecen a la subtribu Hippomaninae de la familia Euphorbiaceae.

Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 g/ml. Coumarins with a cyclized ,-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 g/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.

Condensation of N(3)-dimethylthiosemicarbazide with 2-aminoacetophenone in anhydrous ethanol produces 2-aminoacetophenone-N(3)-dimethylthiosemicarbazone, 1, which is planar with the S1 and N1 atoms in a syn conformation. The amino group forms a bifurcated intramolecular hydrogen bond with the sulfur and the imine nitrogen, and an intermolecular hydrogen bond with the thione sulfur of a second molecule.

La condensación de la N(3)-dimetiltiosemicarbazida con la 2-aminoacetofenona en etanol anhidro produce la 2-aminoacetofenona-N(3)-dimetiltiosemicarbazona, 1, la molécula es plana y los átomos S1 y N1 se encuentran en una conformación syn. El grupo amino forma un enlace de hidrógeno intramolecular bifurcado con el azufre y el nitrógeno de tipo imina, y un enlace de hidrógeno intermolecular con el azufre de una segunda molécula.