RESUMEN
Chagas' disease, caused by the intracellular protozoan Trypanosoma cruzi, is one of the most serious health problems throughout South America. Despite the progress that has been made in the study of its biochemistry and physiology, more efficient chemotherapies to control this parasitic infection are still lacking. In this paper we report the trypanocidal and cytotoxic activities of a series of sesquiterpene lactones, isolated from Asteraceae medicinal plants. The significant trypanocidal activity and high selectivity indexes found for many of the compounds evaluated, prompted us to undertake a quantitative structure-activity relationship study. A model using 3D molecular descriptors allowed us to set up a high correlation of the observed activity and the atomic spatial arrangement of these sesquiterpene lactones closely related to steric parameters.
Asunto(s)
Productos Biológicos/farmacología , Simulación por Computador , Lactonas/farmacología , Sesquiterpenos/farmacología , Tripanocidas/química , Tripanocidas/farmacología , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Lactonas/química , Lactonas/aislamiento & purificación , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Relación Estructura-Actividad , Tripanocidas/aislamiento & purificación , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Viruses belonging to the Flaviviridae family cause clinically significant diseases in humans and animals. This family includes three genera: Pestivirus [including bovine viral diarrhea virus (BVDV)], Flavivirus [including yellow fever virus (YFV), dengue virus, and West Nile virus (WNV)], and Hepacivirus [including hepatitis C virus (HCV)]. BVDV is responsible for major losses in cattle, causing a range of clinical manifestations, and is also a problematic contaminant in the laboratory. Noncytopathic BVDV infection can remain unnoticed and infect laboratory cell lines through its presence in contaminated bovine serum used in cell culture. BVDV is considered to be a valuable surrogate virus model for identifying and characterizing antiviral agents to be used against HCV. In some aspects of viral replication, BVDV is more advantageous than the currently used HCV replicon systems. In this review, we report the design, synthesis, and activity against BVDV of a series of compounds assayed until now.
Asunto(s)
Antivirales/farmacología , Virus de la Diarrea Viral Bovina/efectos de los fármacos , Diseño de Fármacos , Animales , Antivirales/síntesis química , Antivirales/química , Antivirales/uso terapéutico , Diarrea Mucosa Bovina Viral/tratamiento farmacológico , Diarrea Mucosa Bovina Viral/virología , Bovinos , Nucleósidos/síntesis química , Nucleósidos/química , Nucleósidos/farmacologíaRESUMEN
Natural as well as synthetic coumarins have recently drawn much attention due to its broad pharmacological activities. Many coumarins and their derivatives exert anti-coagulant, anti-tumor, anti-viral, anti-inflammatory and anti-oxidant effects, as well as anti-microbial and enzyme inhibition properties. The recognition of key structural features within coumarin family is crucial for the design and development of new analogues with improved activity and for the characterization of their mechanism of action and potential side effects. The different substituents in the coumarin nucleus strongly influence the biological activity of the resulting derivatives. Although some coumarins have been already characterized to evoke a particular biological activity, the challenge would be the design and synthesis of new derivatives with high specific activity for other pharmacological targets and define their mechanism of action to achieve new therapeutic drugs. The present review highlights the current progress in the development of coumarin scaffolds for drug discovery as novel anti-cancer agents. The major challenges about coumarins include the translation of current knowledge into new potential lead compounds and the repositioning of known compounds for the treatment of cancer.
Asunto(s)
Antineoplásicos/química , Cumarinas/química , Antineoplásicos/uso terapéutico , Cumarinas/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
Several polyfunctionalized cyclobutane derivatives have been synthesized using commercial (-)-alpha-pinene and (-)-verbenone as chiral precursors. Thus, oxidative cleavage of these compounds by using ruthenium trichloride afforded quantitatively (-)-cis-pinonic and (-)-cis-pinononic acids, respectively, without epimerization. These products were converted into several types of aldehydes, which are the key intermediates in the synthesis of cyclobutane dehydro amino acids via Wittig-Horner condensations with suitable phosphonates. These reactions are highly stereoselective, affording exclusively (Z) isomers, stereochemistry being assessed by NMR experiments. The obtained dehydro amino acids are polyfunctionalized molecules useful for the synthesis of other alpha-amino acids, with additional chiral centers, whose configuration must be induced by the chirality of the terpene employed as a precursor.