Joana Bravo

Biology-oriented development of novel lipophilic antioxidants with neuroprotective activity

Hydroxycinnamic derivatives based on ferulic and caffeic acids were designed to meet the pharmacokinetic requirements to cross the blood–brain barrier and to display neuroprotective activity within the central nervous system. Biological screening included the assessment of acetylcholinesterase and glycogen synthase kinase 3β inhibition, iron chelation properties, in vitro blood–brain barrier permeability, evaluation of cytotoxicity and neuroprotection against 6-hydroxydopamine induced damage in SH-SY5Y cells. Although the chemical modifications did not significantly alter the in vitro activity of the parent compounds, the results of the PAMPA-BBB assay show that some derivatives have higher diffusion rates and may reach the brain. The majority of the synthesized compounds did not display cytotoxicity and successfully prevent 6-hydroxydopamine damage. In this series, compound 14 stands out as a promising neuroprotective agent combining a number of key features: iron chelation, neuroprotection against oxidative damage, mild acetylcholinesterase activity and ability to permeate the blood–brain barrier. This biology-oriented approach provides new tools for the generation of new chemical entities to tackle the oxidative damage associated with neurodegenerative disorders.

Exploring cinnamic acid scaffold: development of promising neuroprotective lipophilic antioxidants

New lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(II) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 μM). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.

Kepler Rapidly Rotating Giant Stars

Rapidly rotating giant stars are relatively rare and may represent important stages of stellar evolution, resulting from stellar coalescence of close binary systems or accretion of substellar companions by their hosting stars. In the present Letter, we report 17 giant stars observed in the scope of the Kepler space mission exhibiting rapid rotation behavior. For the first time, the abnormal rotational behavior for this puzzling family of stars is revealed by direct measurements of rotation, namely from photometric rotation period, exhibiting a very short rotation period with values ranging from 13 to 55 days. This finding points to remarkable surface rotation rates, up to 18 times the rotation of the Sun. These giants are combined with six others recently listed in the literature for mid-infrared (IR) diagnostics based on Wide-field Infrared Survey Explorer information, from which a trend for an IR excess is revealed for at least one-half of the stars, but at a level far lower than the dust excess emission shown by planet-bearing main-sequence stars.

A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection

Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.Animal models of group-B streptococcal infections are needed to develop effective therapies. Here, Andrade et al. present a mouse model in which the bacteria are transmitted from vaginally colonised pregnant females to their offspring, causing neonatal meningitis and neurological developmental disabilities.