RESUMO
Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic α, ß-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.
Assuntos
Antineoplásicos , Diosgenina , Humanos , Cianocetona , Diosgenina/farmacologia , Esteroides/farmacologia , Antineoplásicos/farmacologia , Oximas/farmacologia , Cetonas/farmacologiaRESUMO
Antecedentes: La oftalmía nodosa (ON) fue descrita por primera vez por Schön en 1861, y desde entonces ha recibido múltiples nombres, ampliando la identificación de los agentes causales. En Colombia no se tienen referencias precisas sobre dichos agentes. Objetivo: Realizar revisión de tema sobre una enfermedad subdiagnosticada como la ON. Material y métodos: Análisis retrospectivo y narrativo de la literatura, a propósito de la publicación de cinco casos diagnosticados con ON en la Clínica Barraquer, Bogotá, Colombia, de enero de 1983 a diciembre de 2020. Resultados: Los pacientes valorados en nuestra institución presentaron resolución completa de los síntomas una vez que se realizó tratamiento descrito de manera oportuna. Conclusiones: La ON es una enfermedad conocida que requiere alta sospecha clínica para ser diagnosticada. Los corticoesteroides tópicos son la primera línea de tratamiento y se recomienda la retirada del cuerpo extraño siempre que sea posible.
Background: Ophthalmia nodosa (ON) was first described by Schön in 1861, and since then it has received multiple names, broadening the identification of the causal agents. In Colombia there are no precise references to these agents. Objective: To perform a review of an underdiagnosed entity such us ON. Material and methods: To report of five patients diagnosed with ON in Clinica Barraquer, Bogotá, Colombia from January 1983 to December 2020. Retrospective and narrative literature analysis. Results: Patients presented complete resolution once the described treatment was carried out on time. Conclusions: ON is a well-known disease that requires a high clinical suspicion to be diagnosed. Topical corticosteroids are the first line of treatment and removal of the foreign body is recommended.
Assuntos
Humanos , Masculino , AdultoRESUMO
A detailed study of the Baeyer-Villiger reaction of 3-ketosteroids has been performed by using m-chloroperoxybenzoic and trifluoroperoxyacetic acids as oxidants. The process was fully regiospecific for 3-keto-5alpha-steroids with the employ of both peracids, and only partially regioselective for 3-keto-5beta-steroids by using trifluoroperoxyacetic acid. Interestingly, the reaction resulted completely unselective for 3-keto-5beta-steroids by using m-chloroperoxybenzoic acid. Theoretical studies were performed to explain the regiochemistry of this process, which is suggested to be controlled by conformational effects in the transition state of the Criegee rearrangement.
Assuntos
Esteroides/química , Estrutura Molecular , OxirreduçãoRESUMO
The sex pheromone of feral sweet potato weevils Cylas formicarius elegantulus from Cuba was found, via solid-phase microextraction analysis, to be identical to (Z)-3-dodecenyl (E)-2-butenoate, a previously reported compound. Females emitted 20 pg pheromone d(-1). In scanning electron microscopy studies carried out on the male antenna, we identified several types of sensilla: sensilla trichoidea of type 1 (ST1) as long hairs (100-150 microm), sensilla trichoidea of type 2 as short hairs (50-60 microm), sensilla basiconica of type 1 as thick pegs (20-25 microm), sensilla basiconica of type 2 as curved pegs (10-15 microm), and sensilla basiconica of type 3 as thin and straight short pegs (15-20 microm). The same types were observed in female antennae but ST1 were far less abundant than in males. Sensilla chaetica were also found on the flagellum subsegments in both sexes. In electrophysiological tests, the crotonate function in the pheromone structure proved to be critical for activity since regular depolarizations (0.6-0.8 mV) were obtained with puffs on 1 microg of the attractant, but not with puffs of the formate, acetate, propionate, or butyrate analogue of the pheromone. In a double dual-choice olfactometer, males showed maximum activity between the 4th and the 8th hr of scotophase at a dose of 50-1000 ng of pheromone. In field tests, a correlation between the contents of the Z,E isomer in the pheromone formulation with activity was noticed, and baits containing this isomer of stereomeric purity >94% showed the highest attractivity. The presence of 5% of the Z,Z isomer in the lure did not induce any synergistic or inhibitory effect, and the alcohol precursor of the pheromone was inactive. The results show that use of a stereomerically pure pheromone may not be necessary in pest control strategies.
Assuntos
Comportamento Animal/efeitos dos fármacos , Eletrofisiologia , Ipomoea batatas/parasitologia , Atrativos Sexuais/farmacologia , Gorgulhos/efeitos dos fármacos , Gorgulhos/fisiologia , Estruturas Animais/efeitos dos fármacos , Estruturas Animais/ultraestrutura , Animais , Cromatografia Gasosa , Cuba , Relação Dose-Resposta a Droga , Esterificação , Feminino , Masculino , Espectrometria de Massas , Atrativos Sexuais/análise , Atrativos Sexuais/síntese química , Atrativos Sexuais/química , Microextração em Fase Sólida , Fatores de TempoRESUMO
Eight new 5beta-hydroxy-spirostan-6-ones bearing hydroxy and amino functions in the A ring, i.e., 3beta-OH, 3alpha-OH, 2beta,3beta-OH, 2alpha,3beta-OH, 3beta-NH2, 2alpha-NH2-3beta-OH, 2beta-NH2-3beta-OH, and 2beta-OH-3beta-NH2, were efficiently synthesized, and their antiecdysteroid activities were evaluated on the metamorphosis bioassay of mosquito Aedes aegypti. To our knowledge, these new steroids represent the first 5beta-hydroxy-spirostanes which have been tested for antiecdysteroid activity in mosquitoes. The higher antagonistic effect was found for compounds bearing the 3beta-hydroxy and 2beta,3beta-dihydroxy functionality, which show promise as environmental friendly insecticides.
Assuntos
Aedes/efeitos dos fármacos , Ecdisteroides/antagonistas & inibidores , Inseticidas/síntese química , Espirostanos/química , Espirostanos/síntese química , Animais , Inseticidas/farmacologia , Metamorfose Biológica/efeitos dos fármacos , Conformação Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Many plant compounds are able to modulate herbivore growth and reproduction by directly interacting with steroid hormones systems. In insects, several classes of phytochemicals, including brassinosteroids and related substances, interfere with molting and reproduction. The effects of the molting-hormone antagonist pesticide DI-31, a brassinosteroid analogue, on Aedes aegypti mosquito larvae were tested in two different exposure scenarios. After static exposure of first-instar larvae, the calculated NOEC, LOEC, and LC(50) values referenced to 19 d were 0.03, 0.036, and 0.04 mg/mL, respectively. Semistatic exposure of fourth-instar larvae revealed them to be slightly less susceptible than the younger larvae (NOEC 0.03 mg/mL, LOEC 0.036 mg/mL, LC(50) 0.049 mg/mL referenced to 19 days). In both cases mortality was immediate and larval development was retarded. This study suggests that A. aegypti could be a useful model for the detection of hormonally active substances such as DI-31.