Facile Synthesis of Gold(III) Aryl–Carbene Metallacycles

New gold­(III) metallacyclic complexes with unprecedented aryl–carbene bidentate ligands have been prepared by the reaction of the cycloaurated gold­(III) complex [AuCl₂(pap-C¹,N)] (pap = 2-(2-pyridylamino)­phenyl) with isocyanide CNR (R = 2-naphthyl (<b>1</b>), cyclohexyl (<b>2</b>), or 2,6-dimethylphenyl (<b>3</b>)). Complexes have been spectroscopically and structurally characterized, showing in some complexes aurophilic gold­(III)···gold­(III) and π–π interactions. In contrast with the starting material these complexes are emissive in the solid state, probably because of the better σ-donor properties of the new bidentate ligands

New Tacrine–4-Oxo-4<i>H</i>-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer’s disease (AD), a new family of tacrine–4-oxo-4<i>H</i>-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4<i>H</i> -chromene was chosen for its radical capture and β-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine–4-oxo-4<i>H</i>-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- <i>N</i>-{10-[(1,2,3,4-tetrahydroacridin-9-yl)­amino]­decyl}-4 <i>H</i>-chromene-2-carboxamide (<b>19</b>) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties

Calidad de planta de Cedrela odorata L. asociada con prácticas culturales de vivero

En México muchas reforestaciones con Cedrela odorata no han tenido un desempeño inicial favorable, principalmente por el uso de planta de baja calidad, por lo que se requieren de alternativas en los viveros forestales que mejoren dicha condición. En el presente trabajo fue examinada la influencia del volumen de envase e hidrogel sobre la morfología, estado nutrimental y desempeño en campo de plántulas de C. odorata. El volumen del envase se manejó a dos niveles: bolsa de polietileno de 500 mL y tubete de plástico de 380 mL; el hidrogel, con tres niveles: adición de 0, 2 y 4 g L-1 de sustrato. Las características de las plántulas se evaluaron en vivero, mediante la determinación de varios indicadores morfológicos de calidad de planta y el uso de nomogramas de análisis de vectores para el diagnóstico del estado del nitrógeno, fósforo y potasio. El desempeño en campo fue medido como supervivencia y crecimiento durante 17 meses, a partir del establecimiento de la plantación. Las plántulas con los mejores atributos fueron las producidas en envases de 500 mL con la adición de hidrogel al sustrato en dosis de 4 g L-1; no obstante, el mejor desempeño en campo correspondió a las producidas en envases de 500 mL sin hidrogel, lo que permite concluir que el volumen de envase tiene un efecto directo en la calidad de planta de C. odorata

New Melatonin–<i>N</i>,<i>N</i>‑Dibenzyl(<i>N</i>‑methyl)amine Hybrids: Potent Neurogenic Agents with Antioxidant, Cholinergic, and Neuroprotective Properties as Innovative Drugs for Alzheimer’s Disease

Here, we describe a new family of melatonin–<i>N</i>,<i>N</i>-dibenzyl­(<i>N</i>-methyl)­amine hybrids that show a balanced multifunctional profile covering neurogenic, antioxidant, cholinergic, and neuroprotective properties at low-micromolar concentrations. They promote maturation of neural stem cells into a neuronal phenotype and thus they could contribute to CNS repair. They also protect neural cells against mitochondrial oxidative stress, show antioxidant properties, and inhibit human acetylcholinesterase (AChE). Moreover, they displace propidium from the peripheral anionic site of AChE, preventing the β-amyloid aggregation promoted by AChE. In addition, they show low cell toxicity and can penetrate into the CNS. This multifunctional profile highlights these melatonin–<i>N</i>,<i>N</i>-dibenzyl­(<i>N</i>-methyl)­amine hybrids as useful prototypes in the research of innovative drugs for Alzheimer’s disease

Structural Investigation of Weak Intermolecular Interactions (Hydrogen and Halogen Bonds) in Fluorine-Substituted Benzimidazoles

The structures of five fluorinated benzimidazoles and one intermediate (an open double amide) have been determined by X-ray crystallography. In the analysis of these heterocycles, particular attention has been paid to N–H···H hydrogen bonds and to fluorine–fluorine intermolecular contacts. Thus, one of the shortest F···F distances ever reported, 2.596(3) Å, has been observed in 4,5,6,7-tetrafluoro-1<i>H</i>-benzimidazole-2­(3<i>H</i>)-one. The ¹³C, ¹⁵N, and ¹⁹F solid-state NMR data for all benzimidazoles are also given

New Acridine Thiourea Gold(I) Anticancer Agents: Targeting the Nucleus and Inhibiting Vasculogenic Mimicry

Two new 1-acridin-9-yl-3-methylthiourea Au­(I) DNA intercalators [Au­(ACRTU)₂]Cl (<b>2</b>) and [Au­(ACRTU) (PPh₃)]­PF₆ (<b>3</b>) have been prepared. Both complexes were highly active in the human ovarian carcinoma cisplatin-sensitive A2780 cell line, exhibiting IC₅₀ values in the submicromolar range. Compounds <b>2</b> and <b>3</b> are also cytotoxic toward different phenotypes of breast cancer cell lines MDA-MB-231 (triple negative), SK-BR-3 (HER2+, ERα–, and ERβ−), and MCF-7 (ER+). Both complexes induce apoptosis through activation of caspase-3 <i>in vitro.</i> While inhibition of some proteins (thiol-containing enzymes) seems to be the main mechanism of action for cytotoxic gold complexes, <b>2</b> and <b>3</b> present a DNA-dependent mechanism of action. They locate in the cell nucleus according to confocal microscopy and transmission electronic microscopy. The binding to DNA resulted to be <i>via</i> intercalation as shown by spectroscopic methods and viscometry, exhibiting a dose-dependent response on topoisomerase I mediated DNA unwinding. In addition, <b>2</b> and <b>3</b> exhibit potent antiangiogenic effects and are also able to inhibit vasculogenic mimicry of highly invasive MDA-MB-231 cells

New Acridine Thiourea Gold(I) Anticancer Agents: Targeting the Nucleus and Inhibiting Vasculogenic Mimicry

Two new 1-acridin-9-yl-3-methylthiourea Au­(I) DNA intercalators [Au­(ACRTU)₂]Cl (<b>2</b>) and [Au­(ACRTU) (PPh₃)]­PF₆ (<b>3</b>) have been prepared. Both complexes were highly active in the human ovarian carcinoma cisplatin-sensitive A2780 cell line, exhibiting IC₅₀ values in the submicromolar range. Compounds <b>2</b> and <b>3</b> are also cytotoxic toward different phenotypes of breast cancer cell lines MDA-MB-231 (triple negative), SK-BR-3 (HER2+, ERα–, and ERβ−), and MCF-7 (ER+). Both complexes induce apoptosis through activation of caspase-3 <i>in vitro.</i> While inhibition of some proteins (thiol-containing enzymes) seems to be the main mechanism of action for cytotoxic gold complexes, <b>2</b> and <b>3</b> present a DNA-dependent mechanism of action. They locate in the cell nucleus according to confocal microscopy and transmission electronic microscopy. The binding to DNA resulted to be <i>via</i> intercalation as shown by spectroscopic methods and viscometry, exhibiting a dose-dependent response on topoisomerase I mediated DNA unwinding. In addition, <b>2</b> and <b>3</b> exhibit potent antiangiogenic effects and are also able to inhibit vasculogenic mimicry of highly invasive MDA-MB-231 cells