RESUMEN
This article describes the synthesis and antimicrobial activity evaluation of new pipemidic acid derivatives. New compounds were obtained on the basis of Mannich reaction of 4,5-disubstituted 1,2,4-triazole-3-thiones with pipemidic acid. Antimicrobial tests revealed high antibacterial activity of obtained derivatives. Gram-negative rods belonging to Enterobacteriaceae family were particularly most sensitive to new pipemidic acid derivatives. Synthesized compounds exhibited very strong activity towards Proteus mirabilis ATCC 12453, Salmonella typhimurium ATCC 14028 and Escherichia coli ATCC 25922. The minimum inhibitory concentrations of new pipemidic acid derivatives which inhibited the growth of these bacteria were 0.98-7.81 µg/ml, 0.98-7.81 µg/ml and 0.98-3.91 µg/ml, respectively. The antibacterial activity of newly synthesized pipemidic acid derivatives in many cases was far better than the activity of substances used as positive controls (nitrofurantoin, cefuroxime, ampicillin and pipemidic acid).
Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Ácido Pipemídico/farmacología , Antibacterianos/síntesis química , Pruebas de Sensibilidad Microbiana , Ácido Pipemídico/análogos & derivados , Ácido Pipemídico/síntesis química , Tionas/química , Triazoles/químicaRESUMEN
The interaction of copper(II) and manganese(II) with pipemidic acid, Hpipem, afforded the complexes [Cu(pipem)(2)(H(2)O)] x 2H(2)O, 1 and [Mn(pipem)(2)(H(2)O)], 2. The new complexes have been characterised by elemental analyses, infrared, UV-vis and X-band EPR spectroscopy in the temperature range from 4 to 300 K. The monoanion, pipem, exhibits O,O ligation through the carbonyl and carboxylato oxygen atoms. Five coordinate square-pyramid configuration has been proposed for 1 and 2, and the fifth apical position is occupied by a coordinated water molecule.
Asunto(s)
Cobre/química , Espectroscopía de Resonancia por Spin del Electrón/métodos , Manganeso/química , Ácido Pipemídico/química , Ácido Pipemídico/síntesis química , Espectrofotometría/métodos , Magnetismo , Modelos Químicos , Modelos Moleculares , Compuestos Organometálicos/química , Oxígeno/química , Espectrofotometría Infrarroja , Temperatura , Rayos UltravioletaRESUMEN
We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Ciprofloxacina/síntesis química , Ciprofloxacina/farmacología , Piperazinas/síntesis química , Piperazinas/farmacología , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/química , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Ciprofloxacina/química , ADN Bacteriano/efectos de los fármacos , Farmacorresistencia Bacteriana , Mutación/genética , Ácido Pipemídico/síntesis química , Ácido Pipemídico/farmacología , Piperazinas/química , Staphylococcus aureus/enzimología , Staphylococcus aureus/genética , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I , Inhibidores de Topoisomerasa IIRESUMEN
Eight new solid complexes of pipemidic acid (PPA) with trichlorizated rare earth metals LaCl(3), CeCl(3), PrCl(3), NdCl(3), SmCl(3), TbCl(3), DyCl(3), and YCl(3) have been synthesized. The complexes were characterized by elemental analyses, IR, NMR, and molar conductance measurements. The general formulas of the complexes are [M(PPA)(4)]Cl(3) (M=Ce(III), Pr(III), Nd(III), Sm(III), Tb(III), Dy(III), Y(III)), and [La(PPA)(4)Cl]Cl(2). At the same time, the antibacterial activities of PPA and four of its complexes were tested. The results show that PPA and its complexes all have inhibitory action against bacteria of Escherichia coli, Bacillus subtilis, Streptococcus pneumoniae, and Pseudomonas aeruginosa but not Staphylococcus aureus. We compared their antibacterial activities and found that the antibacterial activity of [La(PPA)(4)Cl]Cl(2) against S. pneumoniae is much stronger than that of PPA and the other complexes.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Metales de Tierras Raras/química , Ácido Pipemídico/síntesis química , Ácido Pipemídico/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Peso Molecular , Espectrofotometría InfrarrojaRESUMEN
Investigations on new chemotherapeutic drugs have attracted a worldwide interest during the past few years. The pyrimidine derivatives possessing such the activity have a considerable pharmaceutical significance. The works on these compounds are led in various directions, but a particular importance have modifications of the drug Trimetoprime as well as syntheses of new pipemidic acid derivatives and pyrimidines with the amide group.
