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2.
Parasitol Res ; 118(2): 607-615, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30535524

RESUMEN

Trichomoniasis is the most common non-viral sexually transmitted disease worldwide and can lead to serious consequences in reproductive health, cancer, and HIV acquisition. The current approved treatment present adverse effects and drug resistance data on this neglected parasitic infection is underestimated. Chalcones are a family of molecules that present biological applications, such as activity against many pathogenic organisms including protozoan pathogens. Chalcone (1) and three amino-analogues (2-4) were synthesized by Claisen-Schmidt condensation reaction and had their activity evaluated against the parasitic protozoan Trichomonas vaginalis. This bioassay indicated the presence and position of the amino group on ring A was crucial for anti-T. vaginalis activity. Among these, 3'-aminochalcone (3) presented the most potent effect and showed high cytotoxicity against human vaginal cells. On the other hand, 3 was not able to exhibit toxicity against Galleria mellonella larvae, as well as the hemolytic effect on human erythrocytes. Trophozoites of T. vaginalis were treated with 3, and did not present significant reactive oxygen species (ROS) accumulation, but induced a significantly higher ROS accumulation in human neutrophils after co-incubation. T. vaginalis pyruvate:ferredoxin oxidoreductase (PFOR) and ß-tubulin gene expression was not affected by 3.


Asunto(s)
Antiprotozoarios/farmacología , Chalconas/farmacología , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Tricomoniasis/tratamiento farmacológico , Trichomonas vaginalis/efectos de los fármacos , Animales , Antiprotozoarios/síntesis química , Chalconas/síntesis química , Resistencia a Medicamentos , Femenino , Humanos , Pruebas de Sensibilidad Parasitaria , Enfermedades de Transmisión Sexual/parasitología , Tricomoniasis/parasitología , Trofozoítos/efectos de los fármacos
3.
Biomed Pharmacother ; 95: 847-855, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28903180

RESUMEN

Human and bovine trichomoniasis are sexually transmitted diseases (STD) caused by Trichomonas vaginalis and Tritrichomonas foetus, respectively. Human trichomoniasis is the most common non-viral STD in the world and bovine trichomoniasis causes significant economic losses to breeders. Considering the significant impact of the infections caused by these protozoa and the treatment failures, the search for new therapeutic alternatives becomes crucial. In this study the effect of diamines and amino alcohols in the in vitro viability of trichomonads was evaluated. Screening demonstrated the high activity of diamine 4 against these protozoa. Although cytotoxicity against HMVII cell line and slight hemolysis were observed in vitro, the compound showed no toxic effect on the Galleria mellonella in vivo model. Importantly, diamine 4 was active against both trichomonads species at 6h and 24h of incubation, and these effects was reverted by putrescine, a polyamine, suggesting competition for the same metabolic pathway. These findings indicate that the mechanism of action of diamine 4 is through the polyamine metabolism, a pathway distinct from that presented by metronidazole, the drug usually used to treat trichomoniasis and to which resistance is widely reported. These data demonstrate the importance of diamines as potential novel candidates as anti-T. vaginalis and anti-T. foetus agents.


Asunto(s)
Diaminas/farmacología , Poliaminas/metabolismo , Trichomonas vaginalis/efectos de los fármacos , Tritrichomonas foetus/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Cinética , Pruebas de Sensibilidad Microbiana , Modelos Biológicos , Especies Reactivas de Oxígeno/metabolismo , Trichomonas vaginalis/crecimiento & desarrollo , Tritrichomonas foetus/crecimiento & desarrollo
4.
Talanta ; 93: 206-11, 2012 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-22483900

RESUMEN

Stress studies of the broad-spectrum antiparasitic nitazoxanide were conducted in order to isolate and elucidate the major degradation product involved in thermal, acid, alkaline, oxidative and photolytic decomposition of the drug in solution and solid state. The major degradation product was identified and characterized using techniques namely LC-DAD, (1)H NMR, (13)C NMR, IR, and MS/MS. The stability of nitazoxanide raw material and nitazoxanide in tablets and in suspension powder was studied under different conditions and the results suggest the formation of the same deacetylated degradation product occur in all cases. This product was also studied in order to determine the preliminary cytotoxicity in vitro with mononuclear cells. Compared with nitazoxanide, the degradation product showed a higher cytotoxicity at a concentration of 40 µg mL(-1) after 48 h of incubation, under tested conditions. Therefore, stress studies showed that special care must be taken during the preparation, manufacture, and storage of this pharmaceutical drug.


Asunto(s)
Antiparasitarios/química , Antiparasitarios/toxicidad , Tiazoles/análisis , Tiazoles/química , Tiazoles/toxicidad , Pruebas de Toxicidad/métodos , Antiparasitarios/análisis , Supervivencia Celular/efectos de los fármacos , Humanos , Nitrocompuestos , Seguridad
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