RESUMEN
The rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these 'non-antibiotics', as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines. Another chemically and pharmacologically related class is the thioxanthenes, differing in that the aromatic N of the central phenothiazine ring has been replaced by a C atom. Such "carbon-analogues" were primarily synthesized with the hope that these would be devoid of some of the toxic effects of phenothiazines. Intensive studies on syntheses, as well as chemical and pharmacological properties of thioxanthenes, were initiated in the late 1950s. Although a rather close parallelism with respect to structure activity relationships could be observed between phenothiazines and thioxanthenes; several thioxanthenes were synthesized in pharmaceutical industries and applied for human use as neuroleptics. Antibacterial activities of thioxanthenes came to be recognized in the early 1980s in Europe. During the following years, many of these drugs were found not only to be antibacterial agents but also to possess anti-mycobacterial, antiviral (including anti-HIV and anti-SARS-CoV-2) and anti-parasitic properties. Thus, this group of drugs, which has an inhibitory effect on the growth of a wide variety of microorganisms, needs to be explored for syntheses of novel antimicrobial agents. The purpose of this review is to summarize the neuroleptic and antimicrobial properties of this exciting group of bioactive molecules with a goal of identifying potential structures worthy of future exploration.
Asunto(s)
Antibacterianos/farmacología , Antipsicóticos/farmacología , Bacterias/efectos de los fármacos , Trastornos Psicóticos/tratamiento farmacológico , Tioxantenos/farmacología , Animales , Humanos , MicrobiotaRESUMEN
BACKGROUND & OBJECTIVES: There has been an extensive invasion of tuberculosis at the global level by multidrug resistant as well as extensively drug resistant organisms. Attempts to recover the pathogen in pure culture have frequently failed since the specimens are often highly contaminated and also due to use of insufficient or over-active decontamination procedures. Hence in the present study different methods of decontamination were tested to evaluate their independent efficacies for culture of Mycobacterium tuberculosis. METHODS: A total of 359 samples (241 sputum, 59 urine, 50 endometrium biopsy, 9 pus samples) from clinically suspected cases of tuberculosis were subjected to four different methods of decontamination followed by inoculation in Lowenstein-Jensen medium (LJM), and bilayered medium (BLM) and Kirchner's liquid medium (KLM) to determine the influence of differential decontamination processes. Sputum scanty and positive specimens were graded and each sample was subjected to decontamination by four different techniques. RESULTS: Treatment of specimens with 4 per cent NaOH yielded minimum recovery of pure cultures, while use of 2 per cent NaOH produced higher number of contaminants compared to other methods of decontamination. Addition of N-acetyl L-cystein (NALC) coupled with 2 per cent NaOH to the samples for decontamination provided fairly reasonable recovery, but the highest number of M. tuberculosis cultures could be obtained when the specimens were treated with tri-sodium phosphate and benzalkonium (TSPB). Among the sputum positive cases recovery of growth of M. tuberculosis was higher with greater number of bacilli present in the specimens. Regarding the influence of culture media, BLM produced not only rapid growth, but reasonably higher rate of isolation of M. tuberculosis. INTERPRETATION & CONCLUSIONS: Although use of TSPB was found to be an efficient method of decontamination for successful isolation of M. tuberculosis from contaminated samples, both NALC+ 2 per cent NaOH and TSPB also showed significant recovery of M. tuberculosis cultures in BLM that can facilitate early diagnosis and initiation of treatment.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Mycobacterium tuberculosis/efectos de los fármacos , Hidróxido de Sodio/farmacología , Tuberculosis/microbiología , Compuestos de Benzalconio/farmacología , Descontaminación , Endometrio/microbiología , Femenino , Humanos , Mycobacterium tuberculosis/crecimiento & desarrollo , Fosfatos , Esputo/microbiología , Supuración/microbiología , Tuberculosis/patología , Tuberculosis/prevención & control , Orina/microbiologíaRESUMEN
BACKGROUND & OBJECTIVES: Vibrio cholerae produces acute infection by liberating potent enterotoxin, called cholera toxin in human intestine. Cardiovascular drug lacidipine possessing powerful in vitro action against V. cholerae was tested to determine its possible activity against a toxigenic V. cholerae strain in an established animal model. METHODS: In the rabbit intestine four loops were constructed, 3 of which were injected with over night grown V. cholerae 569B culture. Of these, two loops were simultaneously given graded doses (100, 200 µg) of lacidipine, one was left as such for a positive control. The first loop received sterile medium (negative control). After 18 h, contents of all the loops were examined for accumulation of fluid and number of viable cells. RESULTS: Lacidipine when administrated with live V. cholerae 569B, caused a reduction in the number of viable bacteria along with amount of fluid in the loops. The amount of fluid and number of viable cells were much reduced in the loop that had 200 µg of lacidipine than the loop that received 100 µg of the drug. INTERPRETATION & CONCLUSIONS: Lacidipine has distinct inhibitory action against V. cholerae 569B with respect to both viability and production of cholera toxin in the rabbit ileum. Structural modifications of this compound may possibly lead to procurement of new potent antimicrobial drugs.
Asunto(s)
Antiinfecciosos/administración & dosificación , Toxina del Cólera/antagonistas & inhibidores , Cólera/tratamiento farmacológico , Dihidropiridinas/administración & dosificación , Animales , Fármacos Cardiovasculares , Cólera/microbiología , Humanos , Intestinos/microbiología , Conejos , Vibrio cholerae/efectos de los fármacosRESUMEN
The antimicrobial efficacy of methylglyoxal (MG) against several gram-negative bacteria including Escherichia coli has been reported. To determine the mechanism of action of MG, molecular interactions between lipid and MG within the liposomal membrane were also investigated. Multilamellar and unilamellar vesicles were prepared from 1, 2-dipalmitoyl-snglycero-3-phosphocholine (DPPC). The effect of MG on DPPC liposomal membrane was studied by fluorescence spectroscopy and differential scanning calorimetry. The results indicate that MG interacts mainly with the DPPC head group that produces a significant increase in the fluidity of liposomal vesicles, which could be the cause of a fusion/aggregation effect in microbial cells. The agarose gel electrophoresis study with the genomic DNA extracted from E. coli ATCC 25922 revealed that addition of MG could completely degrade this DNA within 1 h, pointing out to their distinctly high degree of sensitivity towards MG. Further, the drug was able to cross the cell membranes, penetrating into the interior of the cell and interacting with DNA for demonstrating antibacterial activity of MG.
Asunto(s)
Antibacterianos/farmacología , Biomimética , ADN Bacteriano/metabolismo , Membranas Artificiales , Piruvaldehído/farmacología , Rastreo Diferencial de Calorimetría , Electroforesis en Gel de Agar , Escherichia coli/genética , Espectrometría de FluorescenciaRESUMEN
The dicarbonyl compound methylglyoxal is a natural constituent of Manuka honey produced from Manuka flowers in New Zealand. It is known to possess both anticancer and antibacterial activity. Such observations prompted to investigate the ability of methylglyoxal as a potent drug against multidrug resistant Pseudomonas aeruginosa. A total of 12 test P. aeruginosa strains isolated from various hospitals were tested for their resistances against many antibiotics, most of which are applied in the treatment of P. aeruginosa infections. Results revealed that the strains were resistant to many drugs at high levels, only piperacillin, carbenicillin, amikacin and ciprofloxacin showed resistances at comparatively lower levels. Following multiple experimentations it was observed that methylglyoxal was also antimicrobic against all the strains at comparable levels. Distinct and statistically significant synergism was observed between methylglyoxal and piperacillin by disc diffusion tests when compared with their individual effects. The fractional inhibitory concentration index of this combination evaluated by checkerboard analysis, was 0.5, which confirmed synergism between the pair. Synergism was also noted when methylglyoxal was combined with carbenicillin and amikacin.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Piperacilina/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Piruvaldehído/farmacología , Antibacterianos/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Piperacilina/administración & dosificación , Piruvaldehído/administración & dosificaciónRESUMEN
BACKGROUND & OBJECTIVE: There is resurgence of tuberculosis in recent years in spite of availability of comprehensive multidrug therapy. Conventional culture media require a long time for the appearance of growth of Mycobacterium tuberculosis, while the other methods are expensive. Hence, a rapid low cost and safe bilayered medium was developed for early growth and sensitivity testing of M. tuberculosis and the results were compared with those on Lowenstein Jensen medium, Middlebrook 7H10 and Kirchner's liquid media. METHODS: A specially designed bilayered medium, consisting of a lower layer of Lowenstein Jensen medium without malachite green and a top layer of Middlebrook 7H 10 medium with added antibiotics and antifungal agents was prepared. Sputum from clinically suspected cases of tuberculosis, pleural fluid and pus samples were inoculated on the bilayered medium along with the inoculation on other conventional media after proper decontamination and concentration of the samples. Antibiotic sensitivity pattern was determined against a few rapidly growing control and test strains by disc diffusion technique and the results could be recorded by 3 to 7 days. RESULTS: Statistically significant (P< 0.001) isolation rate was obtained on this bilayered medium when compared with the other three media, being 81.7 per cent growth by 7 days. Antibiotic sensitivity test could be recorded by 3 days in case of the rapidly growing strains on this medium, and by 7 days in case of M. tuberculosis strains. INTERPRETATION & CONCLUSION: Bilayered medium produced rapid growth earliest by 48 h, higher isolation rates were achieved as compared to the other conventional media and drug sensitivity testing could also be carried out successfully. Thus, the bilayered medium can be used for obtaining early culture report.
Asunto(s)
Técnicas Bacteriológicas/métodos , Medios de Cultivo , Mycobacterium tuberculosis/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Tuberculosis/diagnóstico , Tuberculosis/microbiologíaRESUMEN
Multidrug resistance in Gram-negative bacteria is now known to be primarily caused by overexpression of efflux pumps that extrude unrelated antibiotics from the periplasm or cytoplasm of the bacterium prior to their reaching their intended target. This review focuses on a variety of agents that have been shown to be efflux pump inhibitors (EPIs) and which, if used as 'helper compounds' in combination with antibiotics to which the organism is initially resistant, may produce the required cure. Although not all of the EPIs may serve a helper role owing to their toxicity, they may nevertheless serve as lead compounds.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Infecciones por Bacterias Gramnegativas/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/toxicidad , Inhibidores Enzimáticos/toxicidad , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , HumanosRESUMEN
The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3x10(7) M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 microg/mL (4xMIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 microg/g/day DCL or 150 microg/g/day STM for 4 weeks, administered from 1 day post infection, significantly (P<0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P<0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans.
Asunto(s)
Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Diclofenaco/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Estreptomicina/uso terapéutico , Tuberculosis/tratamiento farmacológico , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/administración & dosificación , Diclofenaco/farmacología , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Pulmón/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana , Bazo/microbiología , Bazo/patología , Estreptomicina/administración & dosificación , Estreptomicina/farmacología , Análisis de SupervivenciaRESUMEN
Diclofenac sodium (Dc), an anti-inflammatory agent, has remarkable inhibitory action both against drug-sensitive and drug-resistant clinical isolates of various Gram-positive and Gram-negative bacteria. The aim of this study was to determine the ability of Dc to protect mice from a virulent Salmonella infection. Dc injected at 1.5 microg/g and 3.0 microg/g mouse body weight significantly protected animals from the lethality of Salmonella infection. As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential for the management of problematic antibiotic-resistant bacterial infections.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Diclofenaco/uso terapéutico , Farmacorresistencia Bacteriana , Animales , Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/toxicidad , Antipsicóticos/farmacología , Recuento de Colonia Microbiana , Medios de Cultivo , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Diclofenaco/toxicidad , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Salmonella enterica/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Estreptomicina/farmacología , Trifluoperazina/farmacologíaRESUMEN
The cardiovascular drug lacidipine was screened in vitro for possible antibacterial activity with respect to 389 Gram-positive and Gram-negative bacterial strains. It was noticed that most bacteria (233) failed to grow at 50-200 microg/mL concentrations of the drug. Some strains were inhibited at even lower concentrations. The bacteria could be arranged according to their decreasing order of sensitivity as follows: Staphylococcus aureus, Vibrio cholerae, Salmonella spp., Shigellae, Escherichia coli, Bacillus spp., Klebsiellae and Pseudomonas spp. Lacidipine was found to be bacteriostatic in nature against S. aureus and V cholerae. When administered to Swiss strain of white mice at doses of 30 and 60 microg/mouse, lacidipine significantly protected the animals challenged with 50 MLD of S. typhimurium NCTC 74. According to the chi-square test, the in vivo data were highly significant (p<0.001).
Asunto(s)
Antibacterianos/farmacología , Fármacos Cardiovasculares/farmacología , Dihidropiridinas/farmacología , Animales , Antibacterianos/química , Antibacterianos/uso terapéutico , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/uso terapéutico , Dihidropiridinas/química , Dihidropiridinas/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Masculino , Ratones , Estructura Molecular , Infecciones por Salmonella/tratamiento farmacológico , Infecciones por Salmonella/microbiología , Pruebas de ToxicidadRESUMEN
The antipsychotic thioxanthene flupenthixol, possessing a trifluoromethyl substituent at position 2, exhibited a distinct antibacterial property against 352 strains of bacteria from 3 Gram-positive and 13 Gram-negative genera. The minimum inhibitory concentration (MIC) of flupenthixol was determined by the National Committee for Clinical Laboratory Standards agar dilution method. MICs ranged from 10-100 microg/mL in most of the strains, whilst some strains were inhibited at even lower concentrations. The mode of action of this drug was found to be bacteriostatic against Staphylococcus aureus and Vibrio cholerae. In the in vivo experiments, this drug was capable of contributing significant protection (P < 0.001) to a Swiss strain of white mice challenged with 50 median lethal dose of a mouse-virulent strain at a drug concentration of 15 microg/mouse. In addition, flupenthixol remarkably reduced the number of viable bacteria in organ homogenates and blood of mice treated with this drug.
Asunto(s)
Antibacterianos/farmacología , Flupentixol/farmacología , Animales , Evaluación Preclínica de Medicamentos/métodos , Flupentixol/química , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Salmonelosis Animal/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Vibrio cholerae/efectos de los fármacosRESUMEN
E. coli is the main agent of uncomplicated urinary tract infections (UTIs) and accounts for more than 85% of recurrent cystitis and at least 35% of recurrent pyelonephritis. Despite the widespread availability of antibiotics, UTIs remain the most common bacterial infection in the human population. It is currently advised that the clinical administration of antibiotics against the pathogenic bacteria should be prohibitted due to the emergence of multidrug resistant (MDR) bacterial strains. Therefore, newer and more effective antimicrobials are in demand to treat such cases. One hundred and thirty six urine samples were collected from UTI patients. E. coli was isolated from 85 samples, out of which 33% were resistant to common antibiotics. The isolates were decreasingly resistant to ampicillin, tobramycin, augmentin, nalidixic acid, cefuroxime, nitrofurantoin, kanamycin, pipemidic acid, chloramphenicol, cefotaxime, cefamendol, ofloxacin, ceftizoxime, norfloxacin and amikacin. The anti-inflammatory drug diclofenac exhibited significant antibacterial activity against common bacterial strains both in vitro and in vivo. The present work was conducted to evaluate the in vitro inhibitory effect of this drug on the clinically isolated strains of E. coli in hospitals. All the isolates were sensitive to diclofenac, with MIC values ranging from 5-50 microg/mL. The MIC90 value of the drug was 25 microg/mL. Therefore, it may be suggested that diclofenac has the capacity to treat UTI caused by E. coli.
Asunto(s)
Antibacterianos/uso terapéutico , Inhibidores de la Ciclooxigenasa/uso terapéutico , Diclofenaco/uso terapéutico , Infecciones por Escherichia coli/terapia , Infecciones Urinarias/tratamiento farmacológico , Animales , Inhibidores de la Ciclooxigenasa/farmacocinética , Diclofenaco/química , Diclofenaco/farmacocinética , Farmacorresistencia Bacteriana , Escherichia coli/genética , Infecciones por Escherichia coli/orina , Humanos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Thepiperazine chlorcyclizine HCl (CCZ), possessing significant antimetabolic as well as virucidal and virustatic activities against the human immunodeficiency virus (HIV) and other retroviruses, was selected to determine its anticarcinogenic potential The anticancer activity of CCZ was evaluated against procarcinogen n-diethylnitrosamine (NDA)-initiated hepatocarcinogenesis, which was subsequently promoted by phenobarbital (PB) in male Sprague-Dawley rats. The anticancer efficacy of CCZ was monitored by estimating some potential markers of neoplastic and preneoplastic hepatic conditions, e.g., glutathione (GSH), glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase (gammaGTP). CCZ exhibited antineoplastic activity on a long-term therapeutic basis. Furthermore, this drug restricted the exponential increase of the antioxidant markers in the hyperplastic nodule and the surrounding liver tissues in comparison with the carcinogen-controlled rats during the entire period of treatment. A decrease in the number of nodules was observed in the CCZ-treated group.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Piperazinas/uso terapéutico , Animales , Carcinógenos/toxicidad , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Dietilnitrosamina/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Fenobarbital/toxicidad , Ratas , Ratas Sprague-DawleyRESUMEN
Methyl-L-DOPA, an antihypertensive agent, has significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. xenopi and M. marinum, and rare pathogens like M. fortuitum. In the present investigation, the screening of the in vitro activity was further extended by testing the in vitro activity against a total of 53 different strains of mycobacteria, including 34 clinical isolates of both drug-sensitive and drug-resistant Mycobacterium tuberculosis. Most of the strains were inhibited at 10-25 microg/mL concentrations of the drug. When methyl-L-DOPA was injected into male mice at a concentration of 10 microg/g body weight (20 g each), methyl-L-DOPA significantly protected them when challenged with a 50 median lethal dose of M. tuberculosis H37Rv102. According to the chi2 test, the in vivo data were highly significant (p<0.01).
Asunto(s)
Antibacterianos/farmacología , Antihipertensivos/farmacología , Levodopa/análogos & derivados , Mycobacterium/efectos de los fármacos , Animales , Farmacorresistencia Bacteriana , Resistencia a Múltiples Medicamentos , Humanos , Levodopa/farmacología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Mycobacterium/clasificación , Mycobacterium/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/tratamiento farmacológicoRESUMEN
The antipsychotic drug prochlorperazine was screened in vitro for possible antimicrobial property against 157 strains of bacteria, belonging to gram positive and gram negative genera. The minimum inhibitory concentration (MIC) of prochlorperazine was determined by agar dilution method, which ranged from 25 to 200 microg/ml with respect to most of the strains. Based on such findings, a further study was undertaken to determine whether the efficacy of this drug could be enhanced in the presence of an antihistaminic agent methdilazine, reported to have remarkable antimicrobial action. Four bacterial strains, sensitive to prochlorperazine as well as to three antibacterial chemotherapeutics, viz., methdilazine, fluphenazine and thioridazine were chosen. Disc diffusion tests with prochlorperazine and methdilazine revealed marked synergism between the combination, compared to their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergism, the checkerboard analysis was performed. The FIC index of this combination turned out to be 0.37, which confirmed synergism. Therefore, this synergistic drug combination might open a new therapeutic approach to combat drug-resistance in bacterial infections.
Asunto(s)
Antipsicóticos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Fenotiazinas/farmacología , Proclorperazina/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Based on its traditional uses in folk medicine, the whole flower extract of Mesua ferrea Linn. was tested for its in vitro antimicrobial efficacy against five different strains of Salmonella spp. All the strains were found to be highly sensitive to the extract, MIC of the extract against each organism being 50 microg/ml. The extract was tested in vitro for its mode of antibacterial activity against S. Typhimurium NCTC 74 and it was found to be bactericidal in action. In vivo studies of this extract offered significant protection to Swiss albino mice at doses approximately 2 and 4 mg/mouse when challenged with 50 median lethal dose of S. Typhimurium NCTC 74. Further, the extract caused statistically significant reduction in viable count of the strain in liver, spleen and heart blood of challenged mice.
Asunto(s)
Clusiaceae/metabolismo , Estructuras de las Plantas/metabolismo , Salmonelosis Animal/tratamiento farmacológico , Infecciones por Salmonella/tratamiento farmacológico , Salmonella typhimurium/metabolismo , Animales , Antiinfecciosos , Relación Dosis-Respuesta a Droga , Corazón/microbiología , Técnicas In Vitro , Hígado/microbiología , Ratones , Extractos Vegetales , Bazo/microbiología , Células Madre , VirulenciaRESUMEN
Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (-) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease.
Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Fenotiazinas/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Clorpromazina/uso terapéutico , Humanos , Mycobacterium tuberculosis/fisiología , Tioridazina/uso terapéutico , Trifluoperazina/uso terapéuticoRESUMEN
The isoflavonoid compounds 'YS11-YS21' were screened for possible antimicrobial property against 12 known Gram-positive and Gram-negative sensitive bacteria. YS11 and YS16 failed to show antimicrobial activity and YS12, 13, 14, 15, 17, 18 and 20 had moderate antimicrobial action. Compounds YS19 and YS21 showed pronounced antimicrobial property. YS19 and YS21 were then tested in vitro against 214 strains of bacteria from one Gram-positive and six Gram-negative genera. The minimum inhibitory concentration (MIC) of YS19 and YS21 was determined by agar dilution method and ranged from 25 to 200 mg/l in most strains. At concentrations of 30 and 60 microg/mouse these compounds offered significant protection to mice challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella Typhimurium.
Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Isoflavonas/farmacología , Animales , Isoflavonas/uso terapéutico , Ratones , Pruebas de Sensibilidad Microbiana , Salmonelosis Animal/tratamiento farmacológico , Salmonella typhimurium/efectos de los fármacosRESUMEN
BACKGROUND & OBJECTIVES: Several compounds are known to possess antimicrobial activity in addition to their predesignated pharmacological actions. In the present study, dicyclomine hydrochloride, an antispasmodic drug, was tested for possible antimicrobial property in vitro and in vivo. METHODS: The minimum inhibitory concentration (MIC) of dicyclomine against the bacteria was determined by agar and broth dilution methods in vitro. The antibacterial activity of dicyclomine was confirmed by animal experiments. Toxicity and protective efficacy of the drug were tested in vivo. RESULTS: Dicyclomine inhibited most of the bacterial isolates tested at 25-100 microg/ml concentration, and a few were sensitive even at a lower concentration (10 microg/ml). Dicyclomine was found to be bacteriostatic in nature against Shigella dysenteriae 7, and bactericidal against S. aureus NCTC 6571, 8530, and 8531. When administered to Swiss white mice at doses of 30 and 60 microg/mouse, dicyclomine protected the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. INTERPRETATION & CONCLUSION: Dicyclomine showed inhibitory action against several pathogenic bacteria. It also offered significant protection to mice against the bacterial challange. As dicyclomine is in routine therapeutic use, it may be developed as a potent antimicrobial agent in many infections.
Asunto(s)
Antibacterianos/farmacología , Diciclomina/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Parasimpatolíticos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Ten cardiovascular drugs, having diverse pharmacological action, were screened for possible antimicrobial property against known eight sensitive bacteria, belonging to Gram positive and Gram negative types. Although five drugs failed to show antimicrobial activity and three had moderate antimicrobial action, oxyfedrine HCl and dobutamine were seen to possess pronounced antimicrobial property. Oxyfedrine was further tested in vitro against 471 strains of bacteria from two Gram positive and fourteen Gram negative genera. The minimum inhibitory concentration (MIC) of oxyfedrine was determined by agar dilution method, which ranged from 50-200 microg/ml in most of the strains, while some strains were inhibited at even lower concentrations. In animal experiments, this compound was capable of offering significant protection to Swiss strain of white mice, challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella typhimurium at concentrations of 15, 30 and 60 microg/mouse. The in vivo results were highly significant according to chi-square test.