RESUMEN
The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of l-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4-9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6-10 and 18-21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6-9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.
Asunto(s)
Antibacterianos/farmacología , Antiparasitarios/farmacología , Hymenolepis nana/efectos de los fármacos , Linezolid/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antiparasitarios/síntesis química , Antiparasitarios/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Linezolid/síntesis química , Linezolid/química , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-ActividadRESUMEN
BACKGROUND: Vitiligo is an acquired pigmentation disorder characterized by melanocyte loss via autoimmune mechanisms triggered by oxidative stress. Gene polymorphisms in antioxidant enzymes and immunomodulators such as catalase (CAT) and vitamin D receptor (VDR), respectively, have been linked to vitiligo in European and Asian populations. Our aim was to evaluate the role of CAT and VDR gene polymorphisms as well as CAT and vitamin D in nonsegmental vitiligo in Northwestern Mexicans. METHODS: A total of 357 subjects, 173 nonsegmental vitiligo patients and 184 age-gender matched healthy controls, were genotyped by PCR-restriction fragment length polymorphism. CAT activity was determined in 39 patients and in 39 controls and vitamin D (VitD) levels in 35 individuals per group. RESULTS: CAT 419 C/T gene polymorphism was not informative, -89 A/T was associated with risk (P = 0.02), and 389 C/T conferred protection against vitiligo along with AT haplotype (P < 0.01 in both cases). VDR BsmI, ApaI, and TaqI gene polymorphisms were not associated with vitiligo, but BsmI was more prevalent in patients with Koebner phenomenon (P = 0.02). Serum CAT activity and VitD levels were lower in patients than in controls, but they showed no association with any vitiligo clinical characteristics neither with their gene polymorphisms. CONCLUSIONS: Our results suggest a role for CAT gene polymorphisms in vitiligo susceptibility in the Mexican population and a lack of association with VDR gene polymorphisms.
Asunto(s)
Catalasa/genética , Predisposición Genética a la Enfermedad , Receptores de Calcitriol/genética , Vitíligo/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Adulto JovenRESUMEN
Red arils of Pithecellobium dulce fruit, commonly known as guamuchil, show high antioxidant (AOx) and α-glucosidase inhibitory (IαG) activities, which have been mainly associated with the content of unknown anthocyanins. In this study, the AOx (i.e., DPPH and ABTS as Trolox equivalents, µmol TE/g) and IαG (as half-maximal inhibitory concentration, IC50, mg/mL) activities of the anthocyanin-rich fraction (ARF) obtained from red arils were contrasted with those of the methanol extract (ME), and the main ARF anthocyanins were characterized by HPLC-DAD-ESI-MS, GC-MS and 1H-NMR. The AOx and IαG values of the ARF (DPPH = 597.8; ABTS = 884.01; IαG = 0.06) were better than those of the ME (DPPH = 41.5; ABTS = 142.3; IαG = 17.5); remarkably, the ARF IαG value was about 42 times lower than that of acarbose. The main anthocyanins in ARF were pelargonidin 3-O-glucoside and cyanidin 3-O-glucoside. Thus, the consumption of red P. dulce arils could provide health benefits for prevention/treatment of chronic degenerative diseases such as diabetes.
Asunto(s)
Antocianinas/análisis , Antocianinas/farmacología , Antioxidantes/farmacología , Fabaceae/química , Inhibidores de Glicósido Hidrolasas/farmacología , Antocianinas/química , Antioxidantes/química , Cromatografía Líquida de Alta Presión , Frutas/química , Cromatografía de Gases y Espectrometría de Masas , Glucósidos/análisis , Glucósidos/farmacología , Inhibidores de Glicósido Hidrolasas/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
C-C chemokine receptor type 5 (CCR5) is known for its role as a co-receptor for HIV-1 infection. Some individuals possess a 32 bp deletion, known as Delta-32 allele which has been reported to confer resistance to HIV-1 infection. In order to estimate the distribution of Delta-32 allele of CCR5 gene, 1034 mestizo individuals from the Northwest of Mexico, including 385 HIV-1-infected individuals, 472 healthy controls and 177 uninfected female sex workers; were examined by allele-specific PCR. There was no statistically significant difference in the frequency of Delta-32 allele between HIV-1 positive and healthy individuals (OR= 1.1, p= 0.6). However, we found a significantly reduced prevalence of CCR5 Delta-32 heterozygous genotype in female patients (OR= 0.084, 95% CI= 0.011 - 0.630, p= 0.002), as well as in allele frequency, compared to male patients. Furthermore, we observed an inverse relationship between allele frequency and the risk of HIV-1 transmission and AIDS progression among female healthy controls, sex workers and HIV-1 infected groups. Our findings support previous data showing Delta-32 as a genetic protective factor against HIV-1 infection in Mexican women, as well as in women from other populations.
Asunto(s)
Alelos , Infecciones por VIH/genética , VIH-1 , Receptores CCR5/genética , Trabajo Sexual , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , México , Persona de Mediana Edad , Oportunidad Relativa , Receptores CCR5/fisiología , Adulto JovenRESUMEN
A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) values were 12.72, 15.05 and 15.31 microg/mL, respectively; these are potential leads for the development of antigiardial compounds.
Asunto(s)
Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Chalconas/síntesis química , Chalconas/farmacología , Giardia lamblia/efectos de los fármacos , Animales , Antiprotozoarios/química , Chalconas/química , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Gnathostomosis is an emerging public health problem in Sinaloa, Mexico, where an increasing number of human cases have been diagnosed since 1989. The present study was carried out to determine the presence of the parasite in other natural hosts from the area. Birds, fish, opossums and raccoons were captured from local dams and lagoons. The flesh from bird and fish specimens was ground and examined under a 100 W light bulb. Larvae were processed for light and electron microscopy. A total of 368 advanced stage 3 (AL3) larvae were found in 300 ichthyophagous birds, with Egretta alba exhibiting the highest infection rate. A total of 4,156 fish were examined, of which six species were infected with AL3 larvae: Arius guatemalensis (blue sea catfish), Dormitator latifrons (Pacific fat sleeper), Gobiomorus sp. (fat sleeper), Oreochromis sp. (Nile tilapia), Cichlasoma beani (Sinaloan cichlid or green guapote) and Eleotris picta (spotted sleeper). Twenty larvae from birds were used to infect domestic cats and dogs. Young adult worms were recovered from the stomach of a cat with a 17 day infection and from a dog with a 35 day infection. Larvae exhibited four rows of hooklets on the head bulb, whereas the young adults had nine rows of hooklets. The cuticular spines of adult worms along the body evolved from single-pointed, bi- or trifurcated spines. Nuclei were counted in intestinal cells examined in serial sections of larvae recovered from a great heron and a fish, in which a mean of 1.6 nuclei/cell was found, corresponding to data published for Gnathostoma binucleatum. Although the external morphology of both larvae and adults are in agreement with previous descriptions of Gnathostoma spinigerum, the results indicate that natural host infections in Sinaloa may be caused by either G. spinigerum or G. binucleatum.