Search results for "design."

Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers

2016

A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the c…

Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors

2021

The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirabl…

Tryptophan-Containing Dual Neuroprotective Peptides: Prolyl Endopeptidase Inhibition and Caenorhabditis elegans Protection from β-Amyloid Peptide Tox…

2018

Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer’s disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition. The inhibitory pe…

Designer Thiopurine-analogues for Optimised Immunosuppression in Inflammatory Bowel Diseases.

2015

Background and Aims: The clinical use of azathioprine and 6-mercaptopurine is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/Rac1 signalling pathway in T lamina propria lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimised suppression of this pathway in inflammatory bowel diseases [IBD]. Methods: Rac1 and Vav1 expressions were analysed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimise Rac1 blockade; 44 modified designer thiopurine-analogues were tested for apoptosis induction, potenti…

Modular device used in the surgery of the human tibia

2018

Efficacy of manual therapy on anxiety and depression in patients with tension-type headache. A randomized controlled clinical trial

2016

Abstract Introduction Tension-type headache (TTH) is a highly prevalent disorder with a significant socio-economic impact. The purpose of this study was to test the efficacy of three manual therapy treatments for reducing TTH-related anxiety and depression. Subjects and methods A clinical trial was conducted on 84 participants diagnosed with tension-type headache forming 4 groups: the first group received suboccipital soft tissue treatment (ST); the second group was treated with articulatory techniques (AT); the third group underwent a combination of both techniques (ST and AT), while the fourth group was the control group. Treatment sessions were administered over four weeks, with post-tre…

Interaction between odorants and proteins involved in the perception of smell: the case of odorant-binding proteins probed by molecular modelling and…

2012

A joint approach that combines molecular modelling and fluorescence spectroscopy is used to study the affinity of an odorant binding protein towards various odorant molecules. We focus on the capability of molecular modelling to rank odorants according to their affinity with this protein, which is involved in the sense of smell. Although ligand-based approaches are unable to propose an accurate model attending to the strength of the bond with the odorant-binding protein, receptor-based structures considering either static or dynamic structure of the protein perform equally to discriminate between good, medium and low affinity odorants. Such approaches will be useful for further rational des…

2019

During speech perception listeners rely on multimodal input and make use of both auditory and visual information. When presented with speech, for example syllables, the differences in brain responses to distinct stimuli are not, however, caused merely by the acoustic or visual features of the stimuli. The congruency of the auditory and visual information and the familiarity of a syllable, that is, whether it appears in the listener’s native language or not, also modulates brain responses. We investigated how the congruency and familiarity of the presented stimuli affect brain responses to audio-visual (AV) speech in 12 adult Finnish native speakers and 12 adult Chinese native speakers. They…

Ensuring Diverse User Experiences and Accessibility While Developing the TeSLA e-Assessment System

2019

The TeSLA project, with its new, innovative approaches for e-assessment, offers a great possibility for increasing the educational equality and making higher education studies available for all. It has been estimated that 10–15% of students in higher education institutions have some disabilities or special educational needs. At online universities or in online programmes, the number is even higher. These numbers emphasise the importance of the universal design for learning as a leading principle while developing the digital learning environments and e-assessment procedures. In this chapter, we describe the key elements of ensuring the accessibility of the TeSLA e-assessment system during th…

[Management of patients with lymphatic diseases and lipoedema during the COVID-19 pandemic. Recommendations of the Spanish Group of Lymphology].

2020

Resumen La pandemia de COVID-19 es un desafío para el manejo de las patologías no COVID como la enfermedad linfática y el lipedema. La Telemedicina puede evitar la propagación del coronavirus. Se necesita un sistema que nos ayude a determinar la prioridad clínica y la selección de la asistencia presencial o telemática para cada paciente y la forma de realizarlas durante la pandemia. El Grupo Español de Linfología (GEL) ha realizado un documento de consenso con recomendaciones basadas en la bibliografía y experiencia clínica, como guía de práctica clínica en el manejo de anomalías linfáticas y lipedema durante la pandemia de COVID-19. Estas recomendaciones deben adaptarse a las característic…