Stretchable Sensor Materials Applicable to Radiofrequency Coil Design in Magnetic Resonance Imaging: A Review.

Wearable sensors are rapidly gaining influence in the diagnostics, monitoring, and treatment of disease, thereby improving patient outcomes. In this review, we aim to explore how these advances can be applied to magnetic resonance imaging (MRI). We begin by (i) introducing limitations in current flexible/stretchable RF coils and then move to the broader field of flexible sensor technology to identify translatable technologies. To this goal, we discuss (ii) emerging materials currently used for sensor substrates, (iii) stretchable conductive materials, (iv) pairing and matching of conductors with substrates, and (v) implementation of lumped elements such as capacitors. Applicable (vi) fabrication methods are presented, and the review concludes with a brief commentary on (vii) the implementation of the discussed sensor technologies in MRI coil applications. The main takeaway of our research is that a large body of work has led to exciting new sensor innovations allowing for stretchable wearables, but further exploration of materials and manufacturing techniques remains necessary, especially when applied to MRI diagnostics.

Design of a volumetric cylindrical coil-tuned at 298 MHz for 7 T imaging.

The concept of a 2D cylindrical High Pass Ladder (2D c-HPL) is used in the development of this ultra high radio frequency (UHRF) volumetric head coil for 7T tuned at the Larmor frequency of 298 MHz. The architecture of the 2D c-HPL helps to overcome the challenges associated with non-uniform magnetic field distribution. The prototype consists of an individual resonating array of inductance-capacitance (LC) elements and each component is tuned to the precise f o frequency. The tuning of the (i) inductance, (ii) capacitance, (iii) mesh size, and (iv) coupling coefficient play critical roles to attain the desired Larmor frequency. For this proof-of-concept, the prototype of a volumetric head coil consists of a cylindrical array size of 4 ×6, with individual LC components of inductance magnitude, 98 nH and four fixed value capacitors and one tunable capacitor that allowed to achieve the desired precession frequency, f r = 298 M H z . The model was tested for three different f o values of 269 MHz, 275 MHz and 286 MHz. The mutual coupling and the eigenfrequencies were compared through bench testing and dispersion equation. The experimental data were in good agreement (< 5%) with the theoretical eigenfrequencies from the dispersion relation. The theoretical eigenfrequencies and the experimental eigenfrequencies are in good agreement for eigenmodes (1,2), (1,3), (2,2), (2,3) and (4,3).

Dual-Channel Stretchable, Self-Tuning, Liquid Metal Coils and Their Fabrication Techniques.

Flexible and stretchable radiofrequency coils for magnetic resonance imaging represent an emerging and rapidly growing field. The main advantage of such coil designs is their conformal nature, enabling a closer anatomical fit, patient comfort, and freedom of movement. Previously, we demonstrated a proof-of-concept single element stretchable coil design with a self-tuning smart geometry. In this work, we evaluate the feasibility of scaling this coil concept to a multi-element coil array and the associated engineering and manufacturing challenges. To this goal, we study a dual-channel coil array using full-wave simulations, bench testing, in vitro, and in vivo imaging in a 3 T scanner. We use three fabrication techniques to manufacture dual-channel receive coil arrays: (1) single-layer casting, (2) double-layer casting, and (3) direct-ink-writing. All fabricated arrays perform equally well on the bench and produce similar sensitivity maps. The direct-ink-writing method is found to be the most advantageous fabrication technique for fabrication speed, accuracy, repeatability, and total coil array thickness (0.6 mm). Bench tests show excellent frequency stability of 128 ± 0.6 MHz (0% to 30% stretch). Compared to a commercial knee coil array, the stretchable coil array is more conformal to anatomy and provides 50% improved signal-to-noise ratio in the region of interest.

A pathway towards a two-dimensional, bore-mounted, volume body coil concept for ultra high-field magnetic resonance imaging.

Lack of a body-sized, bore-mounted, radiofrequency (RF) body coil for ultrahigh field (UHF) magnetic resonance imaging (MRI) is one of the major drawbacks of UHF, hampering the clinical potential of the technology. Transmit field (B1 ) nonuniformity and low specific absorption rate (SAR) efficiencies in UHF MRI are two challenges to be overcome. To address these problems, and ultimately provide a pathway for the full clinical potential of the modality, we have designed and simulated two-dimensional cylindrical high-pass ladder (2D c-HPL) architectures for clinical bore-size dimensions, and demonstrated a simplified proof of concept with a head-sized prototype at 7 T. A new dispersion relation has been derived and electromagnetic simulations were used to verify coil modes. The coefficient of variation (CV) for brain, cerebellum, heart, and prostate tissues after B1 + shimming in silico is reported and compared with previous works. Three prototypes were designed in simulation: a head-sized, body-sized, and long body-sized coil. The head-sized coil showed a CV of 12.3%, a B1 + efficiency of 1.33 µT/√W, and a SAR efficiency of 2.14 µT/√(W/kg) for brain simulations. The body-sized 2D c-HPL coil was compared with same-sized transverse electromagnetic (TEM) and birdcage coils in silico with a four-port circularly polarized mode excitation. Improved B1 + uniformity (26.9%) and SAR efficiency (16% and 50% better than birdcage and TEM coils, respectively) in spherical phantoms was observed. We achieved a CV of 12.3%, 4.9%, 16.7%, and 2.8% for the brain, cerebellum, heart, and prostate, respectively. Preliminary imaging results for the head-sized coil show good agreement between simulation and experiment. Extending the 1D birdcage coil concept to 2D c-HPLs provides improved B1 + uniformity and SAR efficiency.

Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease.

A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC50value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood-brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds.

Evaluation of a Flexible 12-Channel Screen-printed Pediatric MRI Coil.

Background Screen-printed MRI coil technology may reduce the need for bulky and heavy housing of coil electronics and may provide a better fit to patient anatomy to improve coil performance. Purpose To assess the performance and caregiver and clinician acceptance of a pediatric-sized screen-printed flexible MRI coil array as compared with conventional coil technology. Materials and Methods A pediatric-sized 12-channel coil array was designed by using a screen-printing process. Element coupling and phantom signal-to-noise ratio (SNR) were assessed. Subjects were scanned by using the pediatric printed array between September and November 2017; results were compared with three age- and sex-matched historical control subjects by using a commercial 32-channel cardiac array at 3 T. Caregiver acceptance was assessed by asking nurses, technologists, anesthesiologists, and subjects or parents to rate their coil preference. Diagnostic quality of the images was evaluated by using a Likert scale (5 = high image quality, 1 = nondiagnostic). Image SNR was evaluated and compared. Results Twenty study participants were evaluated with the screen-printed coil (age range, 2 days to 12 years; 11 male and nine female subjects). Loaded pediatric phantom testing yielded similar noise covariance matrices and only slightly degraded SNR for the printed coil as compared with the commercial coil. The caregiver acceptance survey yielded a mean score of 4.1 ± 0.6 (scale: 1, preferred the commercial coil; 5, preferred the printed coil). Diagnostic quality score was 4.5 ± 0.6. Mean image SNR was 54 ± 49 (paraspinal muscle), 78 ± 51 (abdominal wall muscle), and 59 ± 35 (psoas) for the printed coil, as compared with 64 ± 55, 65 ± 48, and 57 ± 43, respectively, for the commercial coil; these SNR differences were not statistically significant (P = .26). Conclusion A flexible screen-printed pediatric MRI receive coil yields adequate signal-to-noise ratio in phantoms and pediatric study participants, with similar image quality but higher preference by subjects and their caregivers when compared with a conventional MRI coil. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Lamb in this issue.

Derivatives of the ß-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer's Disease.

Twelve derivatives 1a-1m of the ß-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3ß (GSK-3ß) inhibition potency was evaluated in the active derivatives. In order to reveal the availability of the drugs to the CNS, we elucidated the potential of selected derivatives to penetrate through the blood-brain barrier (BBB). Two compounds, namely 11-O-(2-methylbenzoyl)-haemanthamine (1j) and 11-O-(4-nitrobenzoyl)-haemanthamine (1m), revealed the most intriguing profile, both being acetylcholinesterase (hAChE) inhibitors on a micromolar scale, with GSK-3ß inhibition properties, and predicted permeation through the BBB. In vitro data were further corroborated by detailed inspection of the compounds' plausible binding modes in the active sites of hAChE and hBuChE, which led us to provide the structural determinants responsible for the activity towards these enzymes.

Clinical validation of REALQUALITY RQ-HPV Screen according to the international guidelines for human papillomavirus DNA test requirements for cervical screening.

BACKGROUND: According to international guidelines, HPV DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more severe lesions. The aim of this study was to assess whether REALQUALITY RQ-HPV Screen, a new assay based on real time PCR that targets the E6-E7 region of 14 high-risk human papillomaviruses, meets the criteria for primary cervical cancer screening. METHODS: As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with that of a clinically validated reference test (Hybrid Capture 2, HC2). The reproducibility of the device was assessed as well. The clinical samples used to test the hypothesis of non-inferiority and to asses reproducibility comprised 910 and 536 cervical specimens respectively. All specimens were originating from a population-based screening cohort. RESULTS: The study demonstrates that both the clinical sensitivity and specificity of REALQUALITY RQ-HPV Screen are non-inferior to those of HC2. In addition, an adequate intra- and inter-laboratory reproducibility has been reached by the test. CONCLUSIONS: REALQUALITY RQ-HPV Screen fulfils all the requirements of the international guidelines and can be considered clinically validated for primary cervical cancer screening purposes.

Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives.

The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5 h of carrageenan injection at the 30 mg kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process.

Development and validation of an LC-ESI-MS/MS method for the quantification of D-84, reboxetine and citalopram for their use in MS Binding Assays addressing the monoamine transporters hDAT, hSERT and hNET.

MS Binding Assays represent a label-free alternative to radioligand binding assays. In this study, we present an LC-ESI-MS/MS method for the quantification of (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol [(R,R)-D-84, (R,R)-1], (S,S)-reboxetine [(S,S)-2], and (S)-citalopram [(S)-3] employed as highly selective nonlabeled reporter ligands in MS Binding Assays addressing the dopamine [DAT, (R,R)-D-84], norepinephrine [NET, (S,S)-reboxetine] and serotonin transporter [SERT, (S)-citalopram], respectively. The developed LC-ESI-MS/MS method uses a pentafluorphenyl stationary phase in combination with a mobile phase composed of acetonitrile and ammonium formate buffer for chromatography and a triple quadrupole mass spectrometer in the multiple reaction monitoring mode for mass spectrometric detection. Quantification is based on deuterated derivatives of all three analytes serving as internal standards. The established LC-ESI-MS/MS method enables fast, robust, selective and highly sensitive quantification of all three reporter ligands in a single chromatographic run. The method was validated according to the Center for Drug Evaluation and Research (CDER) guideline for bioanalytical method validation regarding selectivity, accuracy, precision, calibration curve and sensitivity. Finally, filtration-based MS Binding Assays were performed for all three monoamine transporters based on this LC-ESI-MS/MS quantification method as read out. The affinities determined in saturation experiments for (R,R)-D-84 toward hDAT, for (S,S)-reboxetine toward hNET, and for (S)-citalopram toward hSERT, respectively, were in good accordance with results from literature, clearly demonstrating that the established MS Binding Assays have the potential to be an efficient alternative to radioligand binding assays widely used for this purpose so far.

Perioperative analgesic effects of an ultrasound-guided transversus abdominis plane block with a mixture of bupivacaine and lidocaine in cats undergoing ovariectomy.

OBJECTIVE: To evaluate the perioperative analgesic effects of a transversus abdominis plane (TAP) block with a mixture of lidocaine and bupivacaine administered to cats undergoing ovariectomy. STUDY DESIGN: Controlled, randomized, prospective, blinded clinical study. ANIMALS: A group of 20 healthy cats. METHODS: Robenacoxib (2 mg kg-1) was administered subcutaneously 0.5 hour before intramuscular (IM) administration of ketamine (5 mg kg-1), methadone (0.1 mg kg-1) and dexmedetomidine (0.01 mg kg-1). General anesthesia was induced with intravenous (IV) propofol and maintained with isoflurane. An ultrasound-guided TAP block was performed by injecting 0.5% bupivacaine (0.2 mL kg-1) diluted in a total volume of 1.5 mL 2% lidocaine bilaterally (TAP group, n = 10) or the same volume of saline solution bilaterally in controls (CTR group, n = 10). During surgery, a 20% increase in heart rate and respiratory frequency was treated with IV fentanyl (0.001 mg kg-1). Before premedication and at 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours after extubation, pain was assessed with a simple descriptive pain scale, that ranged from 0 (no pain) to 4 (intense pain). For pain scores ≥3, IM methadone (0.1 mg kg-1) was administered. Data were analyzed with the Friedman or the analysis of variance (anova) test, and p < 0.05 was considered statistically significant. RESULTS: Only two cats in the CTR group were administered one dose of fentanyl during surgery. At 2, 6, 8, 12, 16, 20 and 24 hours after surgery, the pain score was higher in the CTR group. A mean dose of 0.5 ± 0.2 mg kg-1 methadone was administered to all cats in the CTR groups within 24 hours. Methadone was not administered to the TAP group (pain score < 3). CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided TAP block can be a reliable adjunctive technique, providing analgesia for up to 24 hours in cats undergoing ovariectomy.

Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3ß Inhibitors.

Glycogen synthase kinase-3ß (GSK-3ß) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and ß-catenin. Recent studies have identified GSK-3ß as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3ß is one of the most attractive targets for medicinal chemists in the discovery, design, and synthesis of new selective potent inhibitors. In the current study, twenty-eight Amaryllidaceae alkaloids of various structural types were studied for their potency to inhibit GSK-3ß. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC50 = 30.00 ± 0.71 µM), masonine (IC50 = 27.81 ± 0.01 µM)}, and lycorine-types {caranine (IC50 = 30.75 ± 0.04 µM)}.

HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin.

The Epidermal Growth Factor Receoptor (EGFR) family member human epidermal growth factor receptor 2 (HER2) is overexpressed in many human epithelial malignancies, representing a molecular target for specific anti-neoplastic drugs. Few data are available on HER2 status in differentiated thyroid cancer (DTC). The present study was aimed to investigate HER2 status in sporadic cancers of follicular cell origin to better clarify the role of this receptor in the stratification of thyroid cancer. By immunohistochemistry and fluorescence in-situ hybridization, HER2 expression was investigated in formalin-fixed paraffin-embedded surgical specimens from 90 DTC patients, 45 follicular (FTC) and 45 papillary (PTC) histotypes. No HER2 immunostaining was recorded in background thyroid tissue. By contrast, overall HER2 overexpression was found in 20/45 (44%) FTC and 8/45 (18%) PTC, with a significant difference between the two histotypes (p = 0.046). Five of the six patients who developed metastatic disease during a median nine-year follow-up had a HER2-positive tumor. Therefore, we suggest that HER2 expression may represent an additional aid to identify a subset of patients who are characterized by a worse prognosis and are potentially eligible for targeted therapy.

Naturally Inspired Molecules as Multifunctional Agents for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aß protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Aß generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the "pharmacophores combination" strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu(2+)-induced ROS formation without any direct neurotoxic effect.

From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold.

In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50=2.49±0.08 µM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.

Multitarget drug discovery for Alzheimer's disease: triazinones as BACE-1 and GSK-3ß inhibitors.

Cumulative evidence strongly supports that the amyloid and tau hypotheses are not mutually exclusive, but concomitantly contribute to neurodegeneration in Alzheimer's disease (AD). Thus, the development of multitarget drugs which are involved in both pathways might represent a promising therapeutic strategy. Accordingly, reported here in is the discovery of 6-amino-4-phenyl-3,4-dihydro-1,3,5-triazin-2(1H)-ones as the first class of molecules able to simultaneously modulate BACE-1 and GSK-3ß. Notably, one triazinone showed well-balanced in vitro potencies against the two enzymes (IC50 of (18.03±0.01) µM and (14.67±0.78) µM for BACE-1 and GSK-3ß, respectively). In cell-based assays, it displayed effective neuroprotective and neurogenic activities and no neurotoxicity. It also showed good brain permeability in a preliminary pharmacokinetic assessment in mice. Overall, triazinones might represent a promising starting point towards high quality lead compounds with an AD-modifying potential.

Design, synthesis, in silico and in vitro screening of 1,2,4-thiadiazole analogues as non-peptide inhibitors of beta-secretase.

Beta-secretase is the key enzyme involved in Alzheimer's disease thus; inhibition of the enzyme can lead to a potential anti-Alzheimer drug. In the search of an effective lead candidate, we have designed non-peptide inhibitor molecules based on amino aromatic heterocyclic motifs specifically, substituted 1,2,4-thiadiazole analogues. In silico modelling was employed to study interaction of the designed ligands in the enzyme active site using molecular docking approach as well as for Absorption, Distribution, Metabolism and Excretion studies. The synthesized analogues were pharmacologically screened using in vitro FRET technique. Overall results indicate that one of the analogues, compound 8 is the most promising one against beta secretase.

Phenolic and Antioxidant Characterization of Fruit By-Products for Their Nutraceuticals and Dietary Supplements Valorization under a Circular Bio-Economy Approach.

Agri-food by-products, obtained as waste from the food industry, negatively impact the global economy and the environment. In order to valorize waste materials from fruit juices and tomato sauces as upcycled materials rich in health-promoting compounds, they were characterized in terms of polyphenolic and protein content. The results obtained were compared with those collected for their final products. The recovery of polyphenols was performed via ultrasound-assisted extraction (UAE). A high-performance liquid chromatography-diode array detector (HPLC-DAD) method was developed and validated to depict the quali-quantitative polyphenolic profile of both the by-products and the final products. The antioxidant capacity of the resulting extracts was characterized by UV-Vis spectrophotometric assays in terms of total phenolic content (TPC) and total antioxidant status (TAS). Moreover, the protein content was assessed with the Kjeldahl method too. The results highlighted a significant quantity of polyphenols remaining in peach, apricot, and apple by-products, which were able to exert an antioxidant activity (in the range of 4.95 ± 5.69 × 10-1 to 7.06 ± 7.96 × 10-1 mmol Trolox 100 g-1 of dry weight (DW) sample). Conversely, the tomato by-products were highly rich in proteins (11.0 ± 2.00 to 14.4 ± 2.60 g of proteins 100 g-1 DW). The results proved that all by-products may potentially be sustainable ingredients with nutritional and functional value in a circular bio-economy prospect.

Integrating a quinone substructure into histone deacetylase inhibitors to cope with Alzheimer's disease and cancer.

Alzheimer's disease (AD) and cancer are among the most devastating diseases of the 21st century. Although the clinical manifestations are different and the cellular mechanisms underlying the pathologies are opposite, there are different classes of molecules that are effective in both diseases, such as quinone-based compounds and histone deacetylase inhibitors (HDACIs). Herein, we investigate the biological effects of a series of compounds built to exploit the beneficial effects of quinones and histone deacetylase inhibition (compounds 1-8). Among the different compounds, compound 6 turned out to be a potent cytotoxic agent in SH-SY5Y cancer cell line, with a half maximal inhibitory concentration (IC50) value lower than vorinostat and a pro-apoptotic activity. On the other hand, compound 8 was nontoxic up to the concentration of 100 µM and was highly effective in stimulating the proliferation of neural precursor cells (NPCs), as well as inducing differentiation into neurons, at low micromolar concentrations. In particular, it was able to induce NPC differentiation solely towards a neuronal-specific phenotype, without affecting glial cells commitment.