RESUMEN
Our first study of tuberculosis in Ferrara during the nineteenth century, whose results have been recently published, focused on disease treatment. Here we present the descriptive analysis of mortality, with the following results being attained: two behavioural patterns are detected with regard to the onset of disease, before and after 1850; TB is a specific disease that affects all parts of the body in all age groups: childhood, and active and passive populations; there are no significant differences with regard to gender; as regards the occupations performed by the deceased, those related to industry and agriculture and to various other activities and services are those with the highest mortality; tuberculosis has a seasonal pattern; summer and autumn are the periods of greatest prevalence (hot weather and humidity are factors that affect the respiratory system); among the forms of tuberculosis it can be observed that up to the year 1850 people died in Ferrara either of pulmonary tuberculosis or TB localised in other areas; from 1851 onward there appears to have been a dramatic change, with a decrease in unspecific diagnosis but the appearance of disease manifestations in its various clinical forms.
Asunto(s)
Salud Pública/historia , Tuberculosis/historia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Humedad , Italia/epidemiología , Pinturas/historia , Prevalencia , Factores de Riesgo , Estaciones del Año , Tuberculosis/epidemiología , Tuberculosis Pulmonar/historiaRESUMEN
Derivatives of pyrazolo[1,5-a][1, 3, 5]triazine-2,4-dione,pyrazolo[1,5-c][1, 3, 5]thiadiazine-2-one, pyrazolo[3,4-d][1, 3]thiazine-4-one, and pyrazolo[3,4-d][1, 3]thiazine-4-thione were screened for antifungal activity against the causal agent of rice blast disease, Magnaporthe grisea. The compounds were tested at doses ranging from 10 to 200mugml(-1), using the commercial fungicide tricyclazole as reference compound. All triazine derivatives inhibited the growth and pigmentation of the mycelia less effectively than tricyclazole. The thiadiazine derivatives proved to be more effective than their triazine counterparts, but only 4-(butylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2h) and 4-(cyclohexylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2j) were more effective than tricyclazole. Pyrazolo[3,4-d][1,3]thiazine-4-one derivatives were active only at the highest doses, whereas members of the pyrazolo[3,4-d][1,3]thiazine-4-thione series inhibited fungal growth at the lowest concentrations used, at which tricyclazole had no effect. A dose-dependent mechanism might be responsible for this effect, with lipophilicity as the governing factor. Within a given set, the presence of a cyclohexyl or an n-butyl group generally increased antifungal activity, with respect to both growth inhibition and cell de-pigmentation of the mycelium, suggesting that a higher lipophilicity might improve transport inside the cells. SEM and TEM of M. grisea hyphae showed that treatment with the most active substance (2h) caused significant ultrastructural effects, particularly on the endomembrane system, suggesting a mechanism of action similar to that of most azole fungicides. Dissimilarities were also observed, with no alterations of the cell wall evident. In conclusion, several compounds showed greater inhibition than tricyclazole, and therefore provide useful new chemistry for control of M. grisea infections.
Asunto(s)
Antifúngicos/farmacología , Azoles/farmacología , Magnaporthe/efectos de los fármacos , Azoles/síntesis química , Azoles/química , Medios de Cultivo , Magnaporthe/crecimiento & desarrollo , Magnaporthe/ultraestructura , Pruebas de Sensibilidad Microbiana/métodos , Microscopía Electrónica de Rastreo , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Pirazoles/farmacología , Tiazoles/farmacologíaRESUMEN
The essential oil extracted by steam distillation from the capitula of Indian Tagetes patula, Asteraceae, was evaluated for its antifungal properties and analyzed by gas chromatography and gas chromatography-mass spectrometry. Thirty compounds were identified, representing 89.1% of the total detected. The main components were piperitone (24.74%), piperitenone (22.93%), terpinolene (7.8%), dihydro tagetone (4.91%), cis-tagetone (4.62%), limonene (4.52%), and allo-ocimene (3.66%). The oil exerted a good antifungal activity against two phytopathogenic fungi, Botrytis cinerea and Penicillium digitatum, providing complete growth inhibition at 10 microl/ml and 1.25 microl/ml, respectively. The contribution of the two main compounds, piperitone and piperitenone, to the antifungal efficacy was also evaluated and ultrastructural modifications in mycelia were observed via electron microscopy, evidencing large alterations in hyphal morphology and a multisite mechanism of action.
Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Aceites de Plantas/química , Aceites de Plantas/farmacología , Tagetes/química , Antifúngicos/aislamiento & purificación , Botrytis/efectos de los fármacos , Botrytis/ultraestructura , Cromatografía de Gases y Espectrometría de Masas , India , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Penicillium/efectos de los fármacos , Aceites de Plantas/aislamiento & purificaciónRESUMEN
The antifungal activity of 3-methyl-5-aminoisoxazole-4-thiocyanate, a new azole derivative, was studied on the dermatophyte Epidermophyton floccosum. The compound strongly inhibited the in vitro growth of two different strains of the fungus and even induced profound morphogenetic anomalies. Optical and electron microscopy showed that such treatment targets the endomembrane system, particularly the plasmalemma, causing abnormal extrusion of the wall mannans. This results in improper arrangement of the different parietal materials; the walls are thus weak and subject to subapical rupture which terminates cell growth and elongation of the hypha. The morphological results and the preliminary biochemical data on fungal sterols suggest that this compound employs an action mechanism similar to that of other azoles used in therapy.
Asunto(s)
Antifúngicos/farmacología , Epidermophyton/efectos de los fármacos , Epidermophyton/metabolismo , Isoxazoles/farmacología , Mananos/metabolismo , Tiocianatos/farmacología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Pared Celular/ultraestructura , Epidermophyton/crecimiento & desarrollo , Epidermophyton/ultraestructura , Microscopía Electrónica , Microscopía Electrónica de RastreoRESUMEN
The antifungal activity of five new synthetic compounds was evaluated on two dermatophytes: Epidermophyton floccosum and Trichophyton rubrum. The data showed that the imidazo-pyrazole and pyrazolo-thiazoles were not particularly effective, while the two pyrazole-thiocyanates proved highly active on both fungi. The most active 5-amino-3-methyl-1-phenylpyrazolo-4-thiocyanate was chosen to perform SEM and TEM morphological studies on both fungi. Both SEM and TEM observations revealed interesting alterations on the two dermatophytes, particularly involving the endomembrane system.
Asunto(s)
Antifúngicos/farmacología , Epidermophyton/efectos de los fármacos , Pirazoles/farmacología , Tiocianatos/farmacología , Trichophyton/efectos de los fármacos , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Epidermophyton/ultraestructura , Microscopía Electrónica de Rastreo , Estructura Molecular , Pirazoles/química , Tiocianatos/química , Trichophyton/ultraestructuraRESUMEN
As a part of an investigation on molecular hybrids as new serine protease inhibitors, the pyrazolo [4,3-c][1,2,5]oxadiazin-3(5H)-one ring system was selected as a model of potential mechanism-based inhibitors. Due to the inherent reactivity of this system an optimal balance between susceptibility to nucleophilic attack and stability in solvents was sought prior to development as therapeutic agents. Substitutions on N5 and C7 of the supporting pyrazole ring with either aliphatic or aromatic groups (compounds 2 a-m) and the replacement of the carbonyl oxygen on the reactive oxadiazinone ring with sulfur (compounds 3a,i) were explored. Two members (2i and 2k) of this class of inhibitors displayed time-dependent inhibition of HLE suggesting mechanism-based inhibition. The observation that HLE generated a product(s) from compound 2i which displayed an identical UV-Visible spectrum to that observed during non-enzymatic hydrolysis further supports this proposal. FlexX-based docking of these compounds into a model of the human leukocyte elastase (HLE) active site produced a molecular model of the inhibitor-enzyme interaction.
Asunto(s)
Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacología , Sitios de Unión , Catepsina G , Catepsinas/antagonistas & inhibidores , Cromatografía Líquida de Alta Presión , Quimotripsina/antagonistas & inhibidores , Estabilidad de Medicamentos , Humanos , Elastasa de Leucocito/antagonistas & inhibidores , Elastasa de Leucocito/química , Elastasa de Leucocito/metabolismo , Modelos Moleculares , Serina Endopeptidasas , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Factores de TiempoRESUMEN
In view of the continuous interest in new DNA cleaving compounds, both for the development of new therapeutic agents and for the possible use as reagents in nucleic acids research, a few pyrazolo[3,4-d][1,2,3]triazole derivatives have been obtained and investigated for their antiproliferative activity and capability to cleave DNA, after light-activation. A possible in situ activation, i.e. in neoplastic tissues, of less cytotoxic derivatives, may lead to potential antitumor compounds endowed with high therapeutic indexes.
Asunto(s)
ADN/efectos de los fármacos , Pirazoles/farmacología , Triazoles/farmacología , Antineoplásicos/farmacología , Antineoplásicos/efectos de la radiación , División Celular/efectos de los fármacos , ADN/metabolismo , Relación Dosis-Respuesta a Droga , Genes myc/genética , Humanos , Concentración 50 Inhibidora , Células Jurkat , Luz , Fotólisis , Regiones Promotoras Genéticas/efectos de los fármacos , Pirazoles/efectos de la radiación , Receptores de Estrógenos/genética , Triazoles/efectos de la radiaciónRESUMEN
The effects of the newly synthesized triazole, 1-amino-6-methyl-4-phenylpyrazolo[3,4-d]-1,2,3-triazole (V5), on the dermatophyte Trichophyton rubrum were tested. Optical and electron microscopy showed that the treatment suppressed the various forms of saprophytic conidia, induced the formation of chlamydospores and accelerated the formation of arthroconidia. This new triazole did not reveal any fungistatic or fungicidal activity and could not be considered as an antifungal substance.
Asunto(s)
Antifúngicos/farmacología , Triazoles/farmacología , Trichophyton/efectos de los fármacos , Microscopía Electrónica , Esporas/ultraestructura , Trichophyton/fisiología , Trichophyton/ultraestructuraRESUMEN
Ever changing problems in agricultural weed control require periodic introduction of new herbicides. Imidazo[4,5-c]pyrazoles, which were considered of interest as potential herbicides, were synthesized and examined for the pre-emergence, post-emergence, and post-transplant control of weeds in rice against broadleaf and grass weed species. The data obtained suggest that some imidazo[4,5-c]pyrazoles have potential herbicidal activity against a wide range of weeds, with 5-methyl, 5-thiomethyl, and 5-unsubstituted derivatives being the most effective. No herbicidal activity was observed in the 5-methylsulfonylimidazo[4,5-c]pyrazole and imidazo[4,5-c]pyrazolone series.
Asunto(s)
Herbicidas/síntesis química , Herbicidas/farmacología , Arabidopsis/efectos de los fármacos , Poaceae/efectos de los fármacos , Pirazoles/síntesis química , Pirazoles/farmacologíaRESUMEN
In view of the biological relevance of triazole-based heterocyclic structures as antifungal, antiviral, and antitumor agents, we have synthesized a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles (2e-h, 2j, 4b) which we evaluated for their cytostatic and antiviral (HIV-1 included) activity and for their capability to inhibit the multiplication of various human pathogenic fungi and bacteria. Moreover, the biological activities of a few compounds, namely pyrazolo[3,4-d]oxazoles (3a-e) and pyrazolo[3,4-d]-1,2,3-triazoles (2a-d, 4a, 5), previously obtained by us but not investigated for their biological activity, were also studied. Only compounds 3a-e were endowed with a significative antiproliferative activity on the human lymphoblastoid cell line MT-4 cells. All pyrazole derivatives proved ineffective in protecting cell cultures against the HIV-1-induced cytopathogenicity, and none of the compounds was active against the bacteria and fungi tested.
Asunto(s)
Antibacterianos/síntesis química , Oxazoles/síntesis química , Triazoles/síntesis química , Antibacterianos/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Oxazoles/farmacología , Triazoles/farmacologíaRESUMEN
The antifungal activity of 4-amino-3-methyl-1-phenylpyrazolo-(3,4-c)isothiazole was studied on Trichophyton rubrum. The compound, at concentrations between 20 and 10 microg ml(-1), induces a remarkable reduction in the growth and causes deep morphogenetic anomalies. The ultrastructural modifications have demonstrated that the compound targets the cell membrane of the fungus, breaking down not only the endomembrane system, but also the 'outer' membrane, with consequent extrusion of materials in the medium. The results suggests a mechanism of action similar to other azoles clinically utilized.
Asunto(s)
Antifúngicos/farmacología , Pirazoles/farmacología , Tiazoles/farmacología , Trichophyton/efectos de los fármacos , Trichophyton/ultraestructura , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Trichophyton/crecimiento & desarrolloRESUMEN
A series of 6-alkyl and 6-arylcarbamoyloximinopyrazolo[3,4-b][1,4]diazepines was prepared and evaluated for fungicidal, insecticidal and herbicidal activity. No one compound showed a general effect but individual compounds exhibited specific activities.
Asunto(s)
Fungicidas Industriales/síntesis química , Herbicidas/síntesis química , Insecticidas/síntesis química , Animales , Fungicidas Industriales/farmacología , Herbicidas/farmacología , Insecticidas/farmacología , Pirazoles/síntesis química , Pirazoles/farmacología , SpodopteraRESUMEN
Two strains of the dermatophyte Epidermophyton floccosum were treated with seven new synthetic azole derivatives to determine their possible antifungal activity. Among these, two diazopyrazoles (1-phenyl-3-methyl-4-diazo-5-methanesulphonamid and 1,3-dimethyl-4-diazo-5-methanesulphonamid) and the triazole (4-methyl-6-t-butylpyrazolo[3,4-d] [1,2,3]triazole) were inactive at the highest dose tested (100 micrograms/ml). The 4-methyl-6-phenyl-pyrazolo[3,4-d] [1,2,3]triazole produced only a partial inhibition of growth, whereas the most active compounds were the two thiadiazines (6H-3-phenyl-5-methyl-7-(3,4-dichlorophenyl)pyrazolo[3,4-c] [1,2,5]thiadiazine-2,2-dioxide and 7-methyl-2-phenyl-4H-pyrazolo[1,5-c] [1,3,5]thiadiazine-4-one), and an aminoisoxazole (3-methyl-5-aminoisoxazole-4-thiocyanate), which induced a remarkable and sometimes complete reduction in the growth rate of the fungus. The structure-activity relationships are discussed.
Asunto(s)
Antifúngicos/farmacología , Azoles/farmacología , Epidermophyton/efectos de los fármacos , Antifúngicos/química , Azoles/química , Epidermophyton/crecimiento & desarrolloRESUMEN
This preliminary research demonstrates the dose dependent antimycotic effect of 3-methyl-5-aminoisoxazole-4-thiocyanate against a number of animal and human dermatophytes. The in vitro results suggest potential medical applications.
Asunto(s)
Arthrodermataceae/efectos de los fármacos , Isoxazoles/farmacología , Tiocianatos/farmacología , Arthrodermataceae/crecimiento & desarrollo , Epidermophyton/efectos de los fármacos , Epidermophyton/crecimiento & desarrollo , Microsporum/efectos de los fármacos , Microsporum/crecimiento & desarrollo , Factores de Tiempo , Trichophyton/efectos de los fármacos , Trichophyton/crecimiento & desarrolloRESUMEN
A series of N-alkyl-N'-(4-diazo-5-pyrazolyl)-ureas (4) was thermally and photochemically converted into pyrazolo [3,4-d][1,2,3]triazole derivatives (5,6) and 5-alkylaminopyrazolo[3,4-d]oxazoles (7) respectively. The products were tested for in vitro antifungal activity against Fusarium culmorum, Botrytis cinerea, Phoma betae, Pythium ultimum, Sclerotinia minor and Rhizoctonia solani. The MIC and ED50 values of compound (6) against some of the test fungi were comparable to those of the reference fungicides iprodione and mancozeb.
Asunto(s)
Hongos/efectos de los fármacos , Fungicidas Industriales/síntesis química , Hidantoínas , Oxazoles/síntesis química , Pirazoles/síntesis química , Triazoles/síntesis química , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Fungicidas Industriales/farmacología , Espectroscopía de Resonancia Magnética , Maneb/farmacología , Oxazoles/farmacología , Pirazoles/farmacología , Espectrofotometría Infrarroja , Triazoles/farmacología , Zineb/farmacologíaRESUMEN
A series of 4-diazo-5-alkylsulphonamidopyrazoles (5) was prepared and tested for antitumor, antiviral and antimicrobial activity. Compounds (5a) and (5b) showed a selective, although not very potent cytostatic activity against L1210 and a human T lymphoblastoid cell line (C8166). Compounds (5a) and (5d-h) showed a selective anti-coxsackie B1 virus activity, whereas 5b was also endowed with some activity against Bacillus subtilis.
Asunto(s)
Antiinfecciosos/síntesis química , Antineoplásicos/síntesis química , Antivirales/síntesis química , Pirazoles/síntesis química , Sulfonamidas/síntesis química , Antibacterianos , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Antivirales/farmacología , Bacterias/efectos de los fármacos , Candida albicans/efectos de los fármacos , Compuestos de Diazonio/síntesis química , Compuestos de Diazonio/farmacología , VIH-1/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Pirazoles/farmacología , Sulfonamidas/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , Ensayo de Placa Viral , Virus/efectos de los fármacosRESUMEN
Starting from 4-thiocarbamoyl-5-aminopyrazoles (I), the AA could prepare two series of products: 4-thiazol-2-yl-5-aminopyrazoles (II) and 4-aminopyrazolo [3,4-c] isothiazoles (III). The screening for in vitro antifungal activity evidenced that compounds (III) are effective in controlling most examined fungi; in particular 1-phenyl-3-methyl-4-aminopyrazolo [3,4-c] isothiazole (III a) at the concentration of 20 p.p.m. completely inhibited the growth of Pythium ultimum and Corticium solani, responsible for the collar rot of the beet.
Asunto(s)
Antifúngicos/síntesis química , Pirazoles/síntesis química , Tiazoles/síntesis química , Fenómenos Químicos , Química , Hongos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Pirazoles/farmacología , Espectrofotometría Ultravioleta , Tiazoles/farmacologíaAsunto(s)
Hipoglucemiantes/síntesis química , Compuestos de Sulfonilurea/síntesis química , Aminoácidos/síntesis química , Aminoácidos/farmacología , Animales , Glucemia/metabolismo , Fenómenos Químicos , Química , Dipéptidos/síntesis química , Dipéptidos/farmacología , Ratas , Compuestos de Sulfonilurea/farmacologíaRESUMEN
Three new series of pyrazolic and pyrazolo-pyrimidinonic derivatives (II a-g), (III a-g) and (IV a-g), containing the substituted phenyl-hydrazide moiety were prepared and studied in order to check some information on the analgesic and antipyretic activity of an analogous series obtained in a previous work. Some derivatives (II b), (II d), (II f), (III b), (III c) and (IV d) show interesting analgesic activity.