RESUMO
The nematocidal in vitro activity of three natural perotetins (phenolic bisbibenzyiethers) and eleven diphenyl ethers used as synthetic precursors has been assayed using two different experimental models, Caenorhabditis elegans and Nippostrongylus brasiliensis. Nine compounds showed some activity against C. elegans and nine against N. brasiliensis. For the former model, three compounds displayed an activity similar to that of the standards, whereas for N. brasiliensis none of the tested compounds was as active as the standards. From the in vitro results, five compounds (3, 4, 8, 9, 13) could be selected as lead compounds to continue the search for improved activity.
Assuntos
Antinematódeos/farmacologia , Bryopsida/química , Fenóis/farmacologia , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Antinematódeos/síntese química , Antinematódeos/isolamento & purificação , Caenorhabditis elegans/efeitos dos fármacos , Dose Letal Mediana , Nippostrongylus/efeitos dos fármacos , Fenóis/síntese química , Fenóis/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: The present study was carried out in seven maternity hospitals to determine the prevalence of maternal syphilis at the time of delivery and the associated risk factors, to conduct a pilot project of rapid syphilis testing in hospital laboratories, to assure the quality of syphilis testing, and to determine the rate of congenital syphilis in infants born to women with syphilis at the time of delivery--all of which would provide baseline data for a national prevention programme in Bolivia. METHODS: All women delivering either live-born or stillborn infants in the seven participating hospitals in and around La Paz, El Alto, and Cochabamba between June and November 1996 were eligible for enrolment in the study. FINDINGS: A total of 61 out of 1428 mothers (4.3%) of live-born infants and 11 out of 43 mothers (26%) of stillborn infants were found to have syphilis at delivery. Multivariate analysis showed that women with live-born infants who had less than secondary-level education, who did not watch television during the week before delivery (this was used as an indicator of socioeconomic status), who had a previous history of syphilis, or who had more than one partner during the pregnancy were at increased risk of syphilis. While 76% of the study population had received prenatal care, only 17% had syphilis testing carried out during the pregnancy; 91% of serum samples that were reactive to rapid plasma reagin (RPR) tests were also reactive to fluorescent treponemal antibody-absorption (FTA-ABS) testing. There was 96% agreement between the results from local hospital laboratories and national reference laboratories in their testing of RPR reactivity of serum samples. Congenital syphilis infection was confirmed by laboratory tests in 15% of 66 infants born to women with positive RPR and FTA-ABS testing. CONCLUSION: These results indicate that a congenital syphilis prevention programme in Bolivia could substantially reduce adverse infant outcomes due to this disease.
Assuntos
Garantia da Qualidade dos Cuidados de Saúde , Sorodiagnóstico da Sífilis/métodos , Sífilis Congênita/prevenção & controle , Sífilis/prevenção & controle , Análise de Variância , Bolívia/epidemiologia , Feminino , Maternidades/normas , Humanos , Recém-Nascido , Laboratórios Hospitalares/normas , Modelos Logísticos , Projetos Piloto , Gravidez , Prevalência , Fatores de Risco , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis Congênita/diagnóstico , Sífilis Congênita/epidemiologiaRESUMO
Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.
Assuntos
Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/síntese química , DNA/química , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Óxidos/síntese química , Óxidos/farmacologia , Aerobiose , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Células Clonais , Citotoxinas/química , Citotoxinas/farmacologia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Oxidiazóis/química , Óxidos/química , Relação Estrutura-AtividadeRESUMO
The title macrocycle, C(31)H(30)O(5), is comprised of two bibenzyl ether moieties linked cyclically by spacers which each consist of two-carbon alkyl chains. The observed conformation of the macrocycle may be partly stabilized by intramolecular C-H.O close contacts. The packing appears to be directed by van der Waals forces. This work explains the occurrence of a signal found in the (1)H NMR spectra of both marchantinquinone and marchantin M trimethyl ether at delta = 5. 49 and 5.56 p.p.m., respectively. The shift in the position of the expected peak can be explained by the proximity of an H atom belonging to one of the aromatic rings to another ring in the same molecule.
RESUMO
As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum. Dose-response studies were done on the more representative compounds (12, 20, and 26). The most active compound, butylcarbamoylbenzo[1,2-c]1,2,5-oxadiazole N-oxide, 26, displayed herbicidal activity at concentrations as low as 24 g/ha.
Assuntos
Herbicidas/síntese química , Óxidos/síntese química , Relação Dose-Resposta a Droga , Herbicidas/farmacologia , Modelos Químicos , Modelos Moleculares , Conformação Molecular , Óxidos/farmacologiaRESUMO
Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypanosomal agents, and some of them, together with the parent compounds, 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives, were also evaluated in vivo using infected mice. Structure-activity relationship studies were carried out using voltammetric response and lipophilic-hydrophilic balance as parameters. Two of the compounds (1 and 3) displayed the highest in vivo activity. A correlation was found between lipophilic-hydrophilic properties and trypanocidal activity, high R(M) values being associated with low in vivo effects.
Assuntos
Aldeídos/síntese química , Furaldeído/análogos & derivados , Compostos de Sulfidrila/síntese química , Tripanossomicidas/síntese química , Aldeídos/farmacologia , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Fenômenos Químicos , Físico-Química , Cromatografia em Camada Fina , Eletroquímica , Furaldeído/síntese química , Furaldeído/farmacologia , Lipídeos/química , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Espectrofotometria Infravermelho , Relação Estrutura-Atividade , Compostos de Sulfidrila/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
In a search for antichagasic drugs, 14 new 4-(nitroarylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide derivatives were synthesized and tested in vitro against the epimastigote form of Trypanosoma cruzi and some of them showed important antiprotozoan activity. Attempts to synthesize new 4-(nitroarylidene)-3,5-diamino-1,2,6-thiadiazine 1,1-dioxides were unsuccessful. The antichagasic properties of nitroarylidene-malononitrile and nitroarylidene-cyanoacetamide derivatives, thus obtained, were also tested. The cytotoxic properties against Vero cells of compounds which showed remarkable in vitro antichagasic activity were evaluated. All compounds tested exhibited high toxicity percentages at 100 micrograms/ml. However, compound 3c showed in vitro antichagasic and cytotoxic properties such as nifurtimox at the dose of 10 micrograms/ml.
Assuntos
Tiadiazinas/síntese química , Tripanossomicidas/síntese química , Animais , Chlorocebus aethiops , Humanos , Espectroscopia de Ressonância Magnética , Nifurtimox/química , Nifurtimox/farmacologia , Nifurtimox/toxicidade , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Nitroimidazóis/toxicidade , Espectrofotometria Infravermelho , Tiadiazinas/farmacologia , Tiadiazinas/toxicidade , Tripanossomicidas/farmacologia , Tripanossomicidas/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Células VeroRESUMO
The syntheses of a new series of derivatives of 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline di-N-oxide are described. In vitro antitrypanosomal activity of these compounds was tested against epimastigote forms of Trypanosoma cruzi. For the most effective drugs, derivatives IIIe and IIIf, the 50% inhibitory dose (ID50) was determined as well as their cytotoxicity against mammalian fibroblasts. Electrochemical studies and ESR spectroscopy show that the highest activities observed are associated with the facile monoelectronation of the N-oxide moiety. Lipophilic-hydrophilic balance of the compounds could also play an important role in their effectiveness as antichagasic drugs.
Assuntos
Óxidos N-Cíclicos/síntese química , Oxidiazóis/síntese química , Tripanossomicidas/síntese química , Animais , Linhagem Celular , Cricetinae , Cricetulus , Óxidos N-Cíclicos/química , Eletroquímica , Espectroscopia de Ressonância de Spin Eletrônica , Fibroblastos , Concentração Inibidora 50 , Oxidiazóis/química , Relação Estrutura-Atividade , Tripanossomicidas/química , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Several novel semicarbazones derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde, and tested in vitro as potential anti-trypanosomal agents. The compounds were prepared in good to excellent yields in 2-3 steps from readily available starting materials. Some derivatives were found to be active against Trypanosoma cruzi with an activity similar to that of Nifurtimox.
Assuntos
Semicarbazonas/síntese química , Tripanossomicidas/síntese química , Animais , Semicarbazonas/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
An intervention to improve maternal and child health was conducted in a remote Bolivian province with limited access to modern medical facilities. The intervention focused on initiating and strengthening women's organizations, developing women's skills in problem identification and prioritization, and training community members in safe birthing techniques. Its impact was evaluated by comparing perinatal mortality rates and obstetric behavior among 409 women before and after the intervention. Perinatal mortality decreased from 117 deaths per 1,000 births before the intervention to 43.8 deaths per 1,000 births after. There was a significant increase in the number of women participating in women's organizations following the intervention, as well as in the number of organizations. The proportion of women receiving prenatal care and initiating breast-feeding on the first day after birth was also significantly larger. The number of infants attended to immediately after delivery likewise increased, but the change was not statistically significant. This study demonstrates that community organization can improve maternal and child health in remote areas.
Assuntos
Mortalidade Infantil , Assistência Perinatal , Resultado da Gravidez , Adolescente , Adulto , Bolívia/epidemiologia , Serviços de Saúde Comunitária , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Serviços de Saúde Materna , Mortalidade Materna , GravidezRESUMO
Screw-worms (Cochliomyia hominivorax Coquerel) constitute a serious plight for livestock in the New World, because they inflict high losses on animals and man. A survey was done by means of an epizootic surveillance system with geographic squares to check for the presence of the insects in Cuba. Screw-worms were detected in 54.8% of myiasis cases all over the island, affecting various animals species, cattle first, followed by swine, sheep and others. Small injuries appeared to be the main enabling factor for screw-worm development. The reasons for the presence of screw-worms without serious consequences on the Cuban livestock are discussed.
Assuntos
Animais Domésticos/parasitologia , Infecção por Mosca da Bicheira/veterinária , Animais , Cuba/epidemiologia , Infecção por Mosca da Bicheira/epidemiologia , Infecção por Mosca da Bicheira/parasitologiaRESUMO
Electrochemical studies (Formal Potentials and Coulometry) were performed on several analogues of Nifurtimox, in order to gain insight on the proposed mechanism of action of these drugs. It is thought that Nifurtimox shows part of its trypanocidal activity via an electron transfer process, leading to the production of active oxygen species that kill the parasite. Formal potentials provide relevant data about the feasibility of electron transfer in vivo. All analogues tested contained the nitro group, which is the most easily reducible group in the parent drug Nifurtimox. The formal potentials values determined ranged from -1.86 to -0.46 V. Coulometric runs were carried out to study the one-electron transfer process. A good correlation between formal potentials and biological activity was found.
Assuntos
Nifurtimox/farmacologia , Animais , Fenômenos Químicos , Físico-Química , Eletroquímica , Transporte de Elétrons , Nifurtimox/química , Relação Estrutura-Atividade , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Two general methods of synthesis have been developed for the preparation of long-chain beta-diketones. The first relies on malonate-type alkylation of acid chlorides derived from fatty acids, while the second, more direct method, involves coupling and subsequent hydrolysis of long-chain acetylenes with acid chlorides of fatty acids.