Synthesis, anti-toxoplasma gondii and antimicrobial activities of 2-hydrazolyl-3-phenyl-5-(4-nitrobenzylidene)-4-thiazolidinone substituted derivatives

A novel series of 2-hydrazolyl-3-phenyl-5-(4-nitrobenzylidene)-4-thiazolidinone substituted (3a-p) has been synthesized. The intermediates 2-hydrazolyl-3-phenyl-4-thiazolidinone substituted (2a-p) were prepared by condensation of benzaldehyde 4-phenyl-3-thiosemicarbazone substituted (1a-p) with ethyl chloroacetate. Theses intermediates were submitted to reaction with ethyl 2-cyano-3-(4-nitrophenyl)-acetate to give the title compounds. The 4-thiazolidinones were screened for their anti-Toxoplasma gondii, and all derivatives promoted decrease of percentage of infection of Vero cells, with elimination of intracellular tachyzoites. The LD50 ranged around 0.5 mM for the intracellular parasites and were higher than 10 mM for Vero cells. According to results of antimicrobial activity, only two compounds showed significant inhibition against M. luteus, but demonstrated higher values of MIC and MBC when compared with standard drug.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis, anti-toxoplasma gondii and antimicrobial activities of 2-hydrazolyl-3-phenyl-5-(4-nitrobenzylidene)-4-thiazolidinone substituted derivatives

A novel series of 2-hydrazolyl-3-phenyl-5-(4-nitrobenzylidene)-4-thiazolidinone substituted (3a-p) has been synthesized. The intermediates 2-hydrazolyl-3-phenyl-4-thiazolidinone substituted (2a-p) were prepared by condensation of benzaldehyde 4-phenyl-3-thiosemicarbazone substituted (1a-p) with ethyl chloroacetate. Theses intermediates were submitted to reaction with ethyl 2-cyano-3-(4-nitrophenyl)-acetate to give the title compounds. The 4-thiazolidinones were screened for their anti-Toxoplasma gondii, and all derivatives promoted decrease of percentage of infection of Vero cells, with elimination of intracellular tachyzoites. The LD50 ranged around 0.5 mM for the intracellular parasites and were higher than 10 mM for Vero cells. According to results of antimicrobial activity, only two compounds showed significant inhibition against M. luteus, but demonstrated higher values of MIC and MBC when compared with standard drug.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Bioequivalence between two metronidazole formulations

Se realizó un estudio de bioequivalencia entre dos formulaciones de Metronidazol 400 mg en comprimidos (EMS-Sigma Pharma como ensayo versus Flagyl - Rhodia como referencia). Una dosis única de 400 mg de cada formulación fue administrada en dos períodos cruzados con un intervalo de siete días entre los dos períodos, a un total de 23 voluntarios jóvenes y sanos. Se utilizó un ensayo por HPLC-UV para determinar las concentraciones plasmáticas de Metronidazol. Los parámetros farmacocinéticos determinados fueron: área bajo la curva de concentraciones vs. tiempo de cero a t (ABC0-t), área bajo la curva de concentraciones vs. tiempo desde cero a infinito (ABC0-∞), concentración plasmá- tica máxima (Cmax), tiempo máximo (Tmax), tiempo de vida media (t1/2) y constante de velocidad de absorción (Ke). La razón de los promedios geométricos del Metronidazole EMS / Flagyl 400 mg fueron 91,04% para ABC0-t, 92,05% para ABC0-∞ y 98,09% para Cmax. Los intervalos de confianza de 90% fueran 85,12 - 97,38%, 85,90 - 98,64% y 90,19 - 106,69 respectivamente. Los IC de 90% para ABC0-t, ABC0-∞ y Cmax estaban en el rango de 80- 125% como ANVISA y la FDA recomienda. En base a nuestros resultados se concluye que las dos formulaciones son bioequivalentes, asumiéndose que tendrían igual eficacia clínicaTwo tablet formulations of 400 mg metronidazole were evaluated for their bioequivalence in twenty three healthy male volunteers (metronidazole, from EMS-Sigma Pharma, Brazil, as the test formulations versus Flagyl® from Rhodia, Brazil, as the reference formulation). A single 400 mg oral dose of each preparation was administered in a randomized two-way crossover design with a seven-day interval between doses. Metronidazole plasma concentrations were determined by the HPLC-UV detection. Pharmacokinetic parameters obtained included AUC0-t , AUC0-∞, Cmax, Tmax, t1/2 , and Ke Geometric mean of . metronidazole / Flagyl® 400 mg individual percent ratio was 91.04% for AUC0-t , 92.05% for AUC0-∞, and 98.09% for Cmax. The 90% confidence intervals were 85.12 - 97.38%, 85.90 - 98.64% and 90.19 - 106.69 respectively. Since the 90% CI for the AUC0-t , AUC0-∞, and Cmax were within the 80-125% interval proposed by ANVISA and by the Food and Drug Administration, and it was concluded that metronidazole 400 mg tablet from EMS-Sigma Pharma was bioequivalent to Flagyl® tablet 400 mg with regard to both the rate and extent of absorptionColegio de Farmacéuticos de la Provincia de Buenos Aire