Hydroxamic Acid Derivatives: From Synthetic Strategies to Medicinal Chemistry Applications

Since the approval of three hydroxamic acid-based HDAC inhibitors as anticancer drugs, such functional groups acquired even more notoriety in synthetic medicinal chemistry. The ability of hydroxamic acids (HAs) to chelate metal ions makes this moiety an attractive metal binding group-in particular, Fe(III) and Zn(II)-so that HA derivatives find wide applications as metalloenzymes inhibitors. In this minireview, we will discuss the most relevant features concerning hydroxamic acid derivatives. In a first instance, the physicochemical characteristics of HAs will be summarized; then, an exhaustive description of the most relevant methods for the introduction of such moiety into organic substrates and an overview of their uses in medicinal chemistry will be presented

Robots for Exploration, Digital Preservation and Visualization of Archeological Sites

Monitoring and conservation of archaeological sites are important activities necessary to prevent damage or to perform restoration on cultural heritage. Standard techniques, like mapping and digitizing, are typically used to document the status of such sites. While these task are normally accomplished manually by humans, this is not possible when dealing with hard-to-access areas. For example, due to the possibility of structural collapses, underground tunnels like catacombs are considered highly unstable environments. Moreover, they are full of radioactive gas radon that limits the presence of people only for few minutes. The progress recently made in the artificial intelligence and robotics field opened new possibilities for mobile robots to be used in locations where humans are not allowed to enter. The ROVINA project aims at developing autonomous mobile robots to make faster, cheaper and safer the monitoring of archaeological sites. ROVINA will be evaluated on the catacombs of Priscilla (in Rome) and S. Gennaro (in Naples)

Effects of Dielectric Stoichiometry on the Photoluminescence Properties of Encapsulated WSe2 Monolayers

Two-dimensional transition-metal-dichalcogenide semiconductors have emerged as promising candidates for optoelectronic devices with unprecedented properties and ultra-compact performances. However atomically thin materials are highly sensitive to surrounding dielectric media, which imposes severe limitations to their practical applicability. Hence for their suitable integration into devices, the development of reliable encapsulation procedures that preserve their physical properties are required. Here, the excitonic photoluminescence of WSe2 monolayer flakes is assessed, at room temperature and 10 K, on mechanically exfoliated flakes encapsulated with SiOx and AlxOy layers employing chemical and physical deposition techniques. Conformal flakes coating on untreated - non-functionalized - flakes is successfully demonstrated by all the techniques except for atomic layer deposition, where a cluster-like oxide coating is observed. No significant compositional or strain state changes in the flakes are detected upon encapsulation by any of the techniques. Remarkably, our results evidence that the flakes' optical emission is strongly influenced by the quality of the encapsulating oxide - stoichiometry -. When the encapsulation is carried out with slightly sub-stoichiometric oxides two remarkable phenomena are observed. First, there is a clear electrical doping of the monolayers that is revealed through a dominant trion - charged exciton - room-temperature photoluminescence. Second, a strong decrease of the monolayers optical emission is measured attributed to non-radiative recombination processes and/or carriers transfer from the flake to the oxide. Power- and temperature-dependent photoluminescence measurements further confirm that stoichiometric oxides obtained by physical deposition lead to a successful encapsulation.Comment: 30 pages, 6 figure

Controversial issues on EEG after sleep deprivation for the diagnosis of epilepsy

EEG after sleep deprivation (SD-EEG) is widely used in many epilepsy centers as an important tool in the epilepsy diagnosis process. However, after more than 40 years of use, there are a number of issues which still need to be clarified concerning its features and role. In particular, the many scientific papers addressing its role in epilepsy diagnosis often differ remarkably from each other in terms of the type of patients assessed, their description and study design. Furthermore, also the length and the type of EEG performed after SD, as well as the length of SD itself, vary dramatically from one study to another. In this paper we shortly underscore the abovementioned differences among the different reports, as well as some interpretations of the findings obtained in the different studies. This analysis emphasizes, if needed, how SD-EEG still represents a crucial step in epilepsy diagnosis, and how additional, controlled studies might further shape its precise diagnostic/prognostic role

Sleep in Frontotemporal Dementia is Equally or Possibly More Disrupted, and at an Earlier Stage, When Compared to Sleep in Alzheimer's Disease

Background: Conversely to other neurodegenerative diseases (i.e., Alzheimer's disease, AD), sleep in frontotemporal dementia (FTD) has not been studied adequately. Although some evidence exists that sleep-wake disturbances occur in FTD, very little is known regarding sleep macrostructure and/or primary sleep disorders. Objective: To investigate these issues in this population and compare them to similar issues in AD and in healthy elderly (HE). Methods: Twelve drug-naïve behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 ± 8.6 years were compared to seventeen drug-naïve AD patients (9 men/8 women) of mean age 69.0 ± 9.9 years and twenty drug-naïve HE (12 men/8 women) of mean age 70.2 ± 12.5 years. All participants were fully assessed clinically, through a sleep questionnaire, an interview, and video-polysomnography recordings. Results: The two patient groups were comparably cognitively impaired. However, compared to FTD patients, the AD patients had a statistically significant longer disease duration. Overall, the sleep profile was better preserved in HE. Sleep complaints did not differ considerably between the two patient groups. Sleep parameters and sleep macrostructure were better preserved in AD compared to FTD patients, regardless of primary sleep disorders, which occurred equally in the two groups. Conclusions: With respect to AD, FTD patients had several sleep parameters similarly or even more affected by neurodegeneration, but in a much shorter time span. The findings probably indicate a centrally originating sleep deregulation. Since in FTD patients sleep disturbances may be obvious from an early stage of their disease, and possibly earlier than in AD patients, physicians and caregivers should be alert for the early detection and treatment of these symptoms

Daytime sleepiness in de novo untreated patients with epilepsy.

The aims of our study were to evaluate excessive daytime sleepiness in a group of de novo untreated people with epilepsy using a comprehensive and standardized approach, including subjective evaluation and neurophysiological and performance tests, and to compare these results with those obtained in a control group. Forty-seven patients with epilepsy (17 affected by primary generalized epilepsy and 30 by partial epilepsy), with a new epilepsy diagnosis and never treated, and 44 controls underwent Multiple Sleep Latency Test (preceded by nocturnal polysomnography), simple/complex visual reaction times, and Epworth Sleepiness Scale evaluation. Newly diagnosed and drug-free patients with epilepsy did not differ from controls in any of the tests performed to evaluate daytime sleepiness. In clinical practice, daytime sleepiness is a well-known and frequent complaint of patients with epilepsy, but different mechanisms and causes, such as associated psychiatric or sleep disorders, nocturnal seizures, sleep fragmentation, and antiepileptic drugs, must be taken into account. Excessive daytime sleepiness should not be considered an unavoidable consequence of epilepsy. Thus, a complete diagnostic work-up in patients with epilepsy and sleepiness should be undertaken whenever possible

Discovery and development of novel salicylate synthase (MbtI) furanic inhibitors as antitubercular agents

We report on the virtual screening, synthesis, and biological evaluation of new furan derivatives targeting Mycobacterium tuberculosis salicylate synthase (MbtI). A receptor-based virtual screening procedure was applied to screen the Enamine database, identifying two compounds, I and III, endowed with a good enzyme inhibitory activity. Considering the most active compound I as starting point for the development of novel MbtI inhibitors, we obtained new derivatives based on the furan scaffold. Among the SAR performed on this class, compound 1a emerged as the most potent MbtI inhibitor reported to date (Ki = 5.3 μM). Moreover, compound 1a showed a promising antimycobacterial activity (MIC99 = 156 μM), which is conceivably related to mycobactin biosynthesis inhibition