Alzheimer’s disease (AD) is a growing global health concern with a massive impact on affected individuals and society. Despite the considerable advances achieved in the understanding of AD pathogenesis, researchers have not been successful in fully identifying the mechanisms involved in disease progression. The amyloid hypothesis, currently the prevalent theory for AD, defends the deposition of β-amyloid protein (Aβ) aggregates as the trigger of a series of events leading to neuronal dysfunction and dementia. Hence, several research and development (R&D) programs have been led by the pharmaceutical industry in an effort to discover effective and safety anti-amyloid agents as disease modifying agents for AD. Among 19 drug candidates identified in the AD pipeline, nine have their mechanism of action centered in the activity of β or γ-secretase proteases, covering almost 50% of the identified agents. These drug candidates must fulfill the general rigid prerequisites for a drug aimed for central nervous system (CNS) penetration and selectivity toward different aspartyl proteases. This review presents the classes of γ-secretase and beta-site APP cleaving enzyme 1 (BACE-1) inhibitors under development, highlighting their structure-activity relationship, among other physical-chemistry aspects important for the successful development of new anti-AD pharmacological agents.

Xanthones are important O-heteroaromatic tricyclic molecules exhibiting a wide range of bioactivities and can represent a showcase to highlight the recent techniques and strategies in organic synthesis towards lead discovery and optimization. This review gives an insight into the recent literature disclosed to obtain the xanthone core, including the drug-like azaxanthones, isosteres of xanthones, by exploiting the optimization of well-known procedures as well as disruptive developed methodologies. With this review, it is expected to provide a useful chemical toolbox to synthetic medicinal chemistry focusing on these privileged structures, covering from 2012 to 2020, with some older examples of azaxanthones.

The ABTS˙⁺ assay, based on reduction of the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical cation, has been automated using flow injection based methods, but biased results are often obtained because the scavenging reaction is not complete upon detection, providing underestimated antioxidant values for samples containing slow reacting compounds. In this work a mesofluidic lab-on-valve (LOV) system was developed to provide fast determination of total antioxidant capacity in a miniaturized fashion. The sample volume was downscaled to 1 μl, with consumption of 97 μl of ABTS (6.8 nmol) per assay. Total antioxidant capacity values for red wines were attained in <1 min by application of the kinetic matching approach, using tannic acid as standard. Calibration curves were linear between 2.5 and 12.5 μM of tannic acid, with a determination throughput of 36 h⁻¹. No statistical difference was found for Trolox equivalent antioxidant capacity (TEAC) values obtained using either an end-point batch-wise microplate method (reaction time of 300 min) or the proposed LOV method.

The rise of multidrug resistance (MDR) bacteria in nosocomial and health-care institutions is widespread and is currently recognized as a major medical challenge. Mechanisms of bacterial resistance, namely, quorum sensing (QS), biofilm formation, and efflux pumps, have been identified as critical biological processes in MDR bacteria. Following previous reports on the activity of phenothiazines against mechanisms of bacterial resistance, in this work we focus on the synthesis of xanthene derivatives aiming to discover phenothiazine bioisosteres with improved activity. Four compounds were obtained from the conjugation of xanthydrol with sulfonamides and aniline and were fully characterized. Their antibacterial activity was assessed considering their minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative strains, efflux pump inhibition, influence on biofilm formation and quorum-sensing (QS) inhibition. It was observed that the MIC of all the tested compounds was above 64 µg/mL The four 9-xanthenyl derivatives obtained, particularly the xanthene sulfonamide derivatives 3b and 3c, showed promising results on QS inhibition with a reduction of pigment production of 48 and 41 mm, and on biofilm formation with a reduction of 78 and 79%, respectively.