Synthesis and Biological Evaluation of Dantrolene-Like Hydrazide and Hydrazone Analogues as Multitarget Agents for Neurodegenerative Diseases

Dantrolene, a drug used for the management of malignant hyperthermia, had been recently evaluated for prospective repurposing as multitarget agent for neurodegenerative syndromes, including Alzheimer's disease (AD). Herein, twenty-one dantrolene-like hydrazide and hydrazone analogues were synthesized with the aim of exploring structure-activity relationships (SARs) for the inhibition of human monoamine oxidases (MAOs) and acetylcholinesterase (AChE), two well-established target enzymes for anti-AD drugs. With few exceptions, the newly synthesized compounds exhibited selectivity toward MAO B over either MAO A or AChE, with the secondary aldimine 9 and phenylhydrazone 20 attaining IC50 values of 0.68 and 0.81 μM, respectively. While no general SAR trend was observed with lipophilicity descriptors, a molecular simplification strategy allowed the main pharmacophore features to be identified, which are responsible for the inhibitory activity toward MAO B. Finally, further in vitro investigations revealed cell protection from oxidative insult and activation of carnitine/acylcarnitine carrier as concomitant biological activities responsible for neuroprotection by hits 9 and 20 and other promising compounds in the examined series

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Search for dark matter annual modulation with DarkSide-50

Dark matter induced event rate in an Earth-based detector is predicted to show an annual modulation as a result of the Earth's orbital motion around the Sun. We searched for this modulation signature using the ionization signal of the DarkSide-50 liquid argon time projection chamber. No significant signature compatible with dark matter is observed in the electron recoil equivalent energy range above $40~{\rm eV_{ee}}$, the lowest threshold ever achieved in such a search.Comment: 8 pages, 4 figure

Search for dark matter-nucleon interactions via Migdal effect with DarkSide-50

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c$^2$ mass dark matter. We present new constraints for sub-GeV/c$^2$ dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12306 $\pm$ 184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c$^2$. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below $3.6$ GeV/c$^2$.Comment: 7 pages, 3 figure

Search for dark matter particle interactions with electron final states with DarkSide-50

We present a search for dark matter particles with sub-GeV/$c^2$ masses whose interactions have final state electrons using the DarkSide-50 experiment's (12306 $\pm$ 184) kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section $\bar{\sigma}_e$, the axioelectric coupling constant $g_{Ae}$, and the dark photon kinetic mixing parameter $\kappa$. We also set the first dark matter direct-detection constraints on the mixing angle $\left|U_{e4}\right|^2$ for keV sterile neutrinos.Comment: 6 pages, 2 figure

DarkSide status and prospects

Sem informaçãoDarkSide uses a dual-phase Liquid Argon Time Projection Chamber to search for WIMP dark matter. The current detector, DarkSide-50, is running since mid 2015 with a target of 50 kg of Argon from an underground source. Here it is presented the latest results of searches of WIMP-nucleus interactions, with WIMP masses in the GeV-TeV range, and of WIMP-electron interactions, in the sub-GeV mass range. The future of DarkSide with a new generation experiment, involving a global collaboration from all the current Argon based experiments, is presented.422-315Sem informaçãoSem informaçãoSem informaçã

DarkSide-50 532-day dark matter search with low-radioactivity argon

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe DarkSide-50 direct-detection dark matter experiment is a dual-phase argon time projection chamber operating at Laboratori Nazionali del Gran Sasso. This paper reports on the blind analysis of a (16 660 +/- 270) kg d exposure using a target of low-radioactivity argon extracted from underground sources. We find no events in the dark matter selection box and set a 90% C. L. upper limit on the dark matter-nucleon spin-independent cross section of 1.14 x 10(-44) cm(2) (3.78 x 10(-44) cm(2), 3.43 x 10(-43) cm(2)) for a WIMP mass of 100 GeV/c(2) (1 TeV/c(2), 10 TeV/c(2)).9810117FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09084-0Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Constraints on sub-GeV dark-matter-electron scattering from the DarkSide-50 experiment

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matterelectron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c(2).1211117FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09084-0Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems of the DS detectors, designed to detect the residual ionization from such collisions