RESUMEN
A multistep synthesis of a new analogue of ketoconazole, which was expected to show antifungal and antibacterial activity, has been described.
Asunto(s)
Adamantano/análogos & derivados , Antibacterianos/farmacología , Antifúngicos/farmacología , Imidazoles/farmacología , Adamantano/síntesis química , Adamantano/farmacología , Antibacterianos/síntesis química , Antifúngicos/síntesis química , Interacciones Farmacológicas , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Imidazoles/síntesis química , Pruebas de Sensibilidad MicrobianaRESUMEN
The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1H-benzimidazoles are reported. There was no substantial difference between antibacterial activities of corresponding 4,6-dichloro- and 4,6-dibromo-derivatives. The present results confirm lower susceptibility to substituted benzimidazoles of Gram-negative compared to Gram-positive bacteria. Minimum inhibitory concentrations (MICs) of a majority of the novel derivatives ranged between 25 and 100microg/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78-50microg/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1H-benzimidazole that were 4-32 times more potent than nitrofurantoin against all Gram-positive bacteria utilized but Escherichia faecalis, against which they were, respectively, 2 and 4 times less potent than nitrofurantoin. Among Gram-negative bacteria used, Stenotrophomonas maltophilia and Bordetella bronchiseptica were most sensitive (as evidenced by a number of MICs =100microg/ml), whereas Pseudomonas aeruginosa was most resistant to the new benzimidazole derivatives (all MICs >400microg/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC(50): 0.006-0.053microg/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC(50): 0.0015-0.182microg/ml) than metronidazole (IC(50): 0.210 and 0.037microg/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections.
Asunto(s)
Antibacterianos/farmacología , Antiprotozoarios/farmacología , Bencimidazoles/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/toxicidad , Antiprotozoarios/síntesis química , Antiprotozoarios/toxicidad , Bencimidazoles/síntesis química , Bencimidazoles/toxicidad , Giardia lamblia/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pruebas de Mutagenicidad , Trichomonas vaginalis/efectos de los fármacosRESUMEN
A series of new derivatives of isoindole in the reaction of nucleophilic substitution with ethyl chloroformate, ethyl bromoacetate and ethyl 3-bromopropanoate were synthesized.
Asunto(s)
Acetatos/química , Formiatos/química , Indoles/química , Propionatos/química , Acetatos/síntesis química , Acetatos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Candida/efectos de los fármacos , Fenómenos Químicos , Química Física , Ésteres/síntesis química , Ésteres/química , Ésteres/farmacología , Formiatos/síntesis química , Formiatos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Indoles/síntesis química , Indoles/farmacología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Propionatos/síntesis química , Propionatos/farmacologíaRESUMEN
Some novel ester imides synthesised from trimellitic acid anhydride and 1-adamantanol or 2-adamantanol, were tested as antimicrobial compounds. Unfortunately, these agents showed a modest antibacterial activity (MIC > 6 microg/ml). However, a comparison of these N-substituted adamantylester imides with the series published previously, indicated that the incorporation of L-alanine and L-phenylalanine into the phthalimide moiety was the best choice regardless of the series and leads to antimicrobial activity against Staphylococcus aureus strains.
Asunto(s)
Adamantano/síntesis química , Adamantano/farmacología , Antibacterianos/síntesis química , Antibacterianos/farmacología , Adamantano/química , Antibacterianos/química , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Antibacterial and antifungal activity of 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles, including a number of newly obtained derivatives, were examined by diffusion method (inhibition area diameter in solid agar medium) and minimum inhibitory concentration (MIC, in liquid and agar medium). Some of the derivatives tested affected fungal colony morphology and exerted genotoxic effects in bacteria. Of the tested compounds, 5,6-dichlorosubstituted derivatives appeared the most active against the majority of microorganisms used.