Polyamine–Drug Conjugates: Do They Boost Drug Activity?

Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments

Distance-Based and Low Energy Adaptive Clustering Protocol for Wireless Sensor Networks

A wireless sensor network (WSN) comprises small sensor nodes with limited energy capabilities. The power constraints of WSNs necessitate efficient energy utilization to extend the overall network lifetime of these networks. We propose a distance-based and low-energy adaptive clustering (DISCPLN) protocol to streamline the green issue of efficient energy utilization in WSNs. We also enhance our proposed protocol into the multi-hop-DISCPLN protocol to increase the lifetime of the network in terms of high throughput with minimum delay time and packet loss. We also propose the mobile-DISCPLN protocol to maintain the stability of the network. The modelling and comparison of these protocols with their corresponding benchmarks exhibit promising results

Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study

Background: Many variables affect outcome after brain injury. Cognitive reserve (CR) is a subjective factor that reflects a set of personal characteristics and that differentiates individuals. It may influence an individual’s capacity to react to brain injury. Objective: To study the effects of cognitive reserve on functional and cognitive outcome at the end of rehabilitation, in patients with severe acquired brain injury (sABI), by means of the Cognitive Reserve Index questionnaire (CRIq). Methods: We report a retrospective study of a continuous series of sABI patients on first admission to a rehabilitation center. Disability and cognitive outcomes were recorded. Results: In the 94 patients enrolled, the assessments after rehabilitation showed a significant gain measured with the disability Rating Scale for patients with a higher CR (CRIq≥ 85). A significant negative correlation was found: between CRIq scores and the interval elapsing before first access to neuropsychological assessment, between CRIq scores, especially level of education, and tests that measure the same domain (attention). Conclusions: Improvements in overall and cognitive disability emerged, but CR did not seem to substantially influence outcome in this sample of patients. This result may be partly due to the clinical severity of the population studied and the sample’s dimension, although quantitatively representative of the population

A heuristic algorithm for finding attractive fixed-length circuits in street maps

In this paper we consider the problem of determining fixed-length routes on a street map that start and end at the same location. We propose a heuristic for this problem based on finding pairs of edge-disjoint shortest paths, which can then be combined into a circuit. Various heuristics and filtering techniques are also proposed for improving the algorithm’s performance

From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2-7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI50 < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity

On-surface Photochemistry of Pre-ordered 1-Methyl-2-phenyl-acetylenes: C-H Bond Activation and Intermolecular Coupling on Highly Oriented Pyrolytic Graphite

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimIn this contribution we report on light-induced metal-free coupling of propynylbenzene molecular units on highly oriented pyrolytic graphite. The reaction occurs within the self-assembled monolayer and leads to the generation of covalently coupled 1,5-hexadiyne and para-terphenyl derivatives under topological control. Such photochemical uncatalysed pathway represents an original approach in the field of topological C−C coupling at the solid/liquid interface and provides new insight into the low temperature formation of aromatic compounds at the surface of carbonaceous supports11Nsciescopu

Prevention and cure of rhinogenous deafness at the Thermal Baths ?Bagni delle Galleraie?

Introduction. Hearing is foundamental for human social life.Secretory Otitis Media (SOM) is the most important cause oftrasmissive hypoacusis in early childhood.Methods. The Hygiene Institute in the University of Siena incollaboration with the Thermal Baths ?Bagni delleGalleraie? proposed a prevention and cure campaign ofrhinogenous deafness in June 2002 in some primary schoolsin the Colle val D?Elsa district. A sample of 87 children wasinvolved in the study (average age of 5,64 ± 1,41 years). Onentering the thermal baths a questionnaire was administeredto the parents, to point out possible risk factors. Results.Results. Among the 87 children, 28 cases of SOM and 21cases of severe tubal disorder were found. Only 19 cases out of 49 were already known to the parents and only 28 joinedthe study and were examined for three years consecutively. Discussion. Out of the 35 children examined in 2002, 28 returned to ?The Galleraie? for the two following years. Theyrepeated the thermal cure for two years as a preventive measure. At present they are not affected by SOM and during thewinters suffered a lower number of infections in the primaryairways and took less antibiotics.Conclusions. Our study focuses on infant school childrenbecause of their critical age for linguistic and social development. Early diagnosis and therapy prevent any negativesocial development

Galantamine-memantine hybrids for Alzheimer's disease: The influence of linker rigidity in biological activity and pharmacokinetic properties

Neurodegenerative processes characterizing Alzheimer's disease (AD) are strictly related to the impairment of cholinergic and glutamatergic neurotransmitter systems which provoke synaptic loss. These experimental evidences still represent the foundation of the actual standard-of-care treatment for AD, albeit palliative, consisting on the coadministration of an acetylcholinesterase inhibitor and the NMDAR antagonist memantine. In looking for more effective treatments, we previously developed a series of galantamine-memantine hybrids where compound 1 (ARN14140) emerged with the best-balanced action toward the targets of interest paired to neuroprotective efficacy in a murine AD model. Unfortunately, it showed a suboptimal pharmacokinetic profile, which required intracerebroventricular administration for in vivo studies. In this work we designed and synthesized new hybrids with fewer rotatable bonds, which is related to higher brain exposure. Particularly, compound 2, bearing a double bond in the tether, ameliorated the biological profile of compound 1 in invitro studies, increasing cholinesterases inhibitory potencies and selective antagonism toward excitotoxic-related GluN1/2B NMDAR over beneficial GluN1/2A NMDAR. Furthermore, it showed increased plasma stability and comparable microsomal stability in vitro, paired with lower half-life and faster clearance in vivo. Remarkably, pharmacokinetic evaluations of compound 2 showed a promising increase in brain uptake in comparison to compound 1, representing the starting point for further chemical optimizations

Tunable Band Alignment with Unperturbed Carrier Mobility of On-Surface Synthesized Organic Semiconducting Wires

The tunable properties of molecular materials place them among the favorites for a variety of future generation devices. In addition, to maintain the current trend of miniaturisation of those devices, a departure from the present top-down production methods may soon be required and self-assembly appears among the most promising alternatives. On-surface synthesis unites the promises of molecular materials and of self assembly, with the sturdiness of covalently bonded structures: an ideal scenario for future applications. Following this idea, we report the synthesis of functional extended nanowires by self-assembly. In particular, the products correspond to one-dimensional organic semiconductors. The uniaxial alignment provided by our substrate templates allows us to access with exquisite detail their electronic properties, including the full valence band dispersion, by combining local probes with spatial averaging techniques. We show how, by selectively doping the molecular precursors, the product\u2019s energy level alignment can be tuned without compromising the charge carrier\u2019s mobility