RESUMEN
OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.
Asunto(s)
Antituberculosos/uso terapéutico , Oxadiazoles/uso terapéutico , Tuberculosis/tratamiento farmacológico , Animales , Antituberculosos/farmacología , Antituberculosos/toxicidad , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana , Femenino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Pruebas de Mutagenicidad , Mycobacterium tuberculosis/efectos de los fármacos , Oxadiazoles/farmacología , Oxadiazoles/toxicidad , Tuberculosis/microbiologíaRESUMEN
Within the United States, cancer is the second leading cause of death by disease among adults and children alike. Although cancer has been characterized as primarily a disease of aging, there is growing awareness that many of the cancer risk factors have their origins earlier in life. In keeping with the current trend of pediatricians assuming the primary care responsibility of adolescents and young adults, this article reviews the current status of primary and secondary cancer prevention as it relates to pediatric practice.