A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.

Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.

Material And Method: Here, we used the tail approach to design a new series of monoaryl () and bicyclic () benzensulfonamide derivatives CA IX and CA XII inhibitors.

Special Issue "Advances in Drug Discovery and Synthesis".

In modern medicinal chemistry, drug discovery is a long, difficult, highly expensive and highly risky process for the identification of new drug compounds [...

Dimolybdenum (II,II) paddlewheel complexes bearing non-steroidal anti-inflammatory drug ligands: Insights into the chemico-physical profile and first biological assessment.

Multinuclear complexes are metal compounds featured by adjacent bound metal centers that can lead to unconventional reactivity. Some ML-type paddlewheel dinuclear complexes with monoanionic bridging ligands feature promising properties, including therapeutic ones. Molybdenum has been studied for the formation of multiple-bonded M compounds due to their unique scaffold, redox, and spectroscopic properties as well as for applications in several fields including catalysis and biology.

Efficacy and Safety of Chemotherapy after Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.

There are currently few data about the safety and effectiveness of chemotherapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed from prior immunotherapy. Data from patients with consecutive stage IIIB-IV, ECOG performance status (PS) 0-2, non-small-cell lung cancer (NSCLC) treated with combination or single-agent chemotherapy following progression on an earlier immunotherapy regimen were retrospectively gathered. Recorded were baseline attributes, outcome metrics, and toxicities.

A dosiomics approach to treatment outcome modeling in carbon ion radiotherapy for skull base chordomas.

Purpose: To investigate the role of dosiomics features extracted from physical dose (D), RBE-weighted dose (D) and dose-averaged Linear Energy Transfer (LET), to predict the risk of local recurrence (LR) in skull base chordoma (SBC) treated with Carbon Ion Radiotherapy (CIRT). Thus, define and evaluate dosiomics-driven tumor control probability (TCP) models.

Materials And Methods: 54 SBC patients were retrospectively selected for this study.

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

Purpose: To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent.

Methods: We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.

Proteolytically Stable Diaza-Peptide Foldamers Mimic Helical Hot Spots of Protein-Protein Interactions and Act as Natural Chaperones.

A novel class of peptidomimetic foldamers based on diaza-peptide units are reported. Circular dichroism, attenuated total reflection -Fourier transform infrared, NMR, and molecular dynamics studies demonstrate that unlike the natural parent nonapeptide, the specific incorporation of one diaza-peptide unit at the N-terminus allows helical folding in water, which is further reinforced by the introduction of a second unit at the C-terminus. The ability of these foldamers to resist proteolysis, to mimic the small helical hot spot of transthyretin-amyloid β (Aβ) cross-interaction, and to decrease pathological Aβ aggregation demonstrates that the introduction of diaza-peptide units is a valid approach for designing mimics or inhibitors of protein-protein interaction and other therapeutic peptidomimetics.

Patient experiences and outcomes in a virtual healing setting: A feasibility study.

Research Questions: How do participants with anxiety receiving distance healing using tuning forks, experience healing sessions? What outcomes do they spontaneously report?

Theoretical Framework: Modified grounded theory, using single interviews to learn about experiences with distant sound healing.

Methodology: Standardized open-ended, qualitative interviews of 30-minute length were conducted after the intervention and analyzed using an inductive and iterative process for identifying themes, categories, and patterns in qualitative data.

Context: Single-arm, pilot feasibility study of Biofield Tuning (BT) for anxiety during the COVID-19 pandemic delivered at a distance facilitated by Zoom (without video).

The role of particle radiotherapy in the treatment of skull base tumors.

The skull base is an anatomically and functionally critical area surrounded by vital structures such as the brainstem, the spinal cord, blood vessels, and cranial nerves. Due to this complexity, management of skull base tumors requires a multidisciplinary approach involving a team of specialists such as neurosurgeons, otorhinolaryngologists, radiation oncologists, endocrinologists, and medical oncologists. In the case of pediatric patients, cancer management should be performed by a team of pediatric-trained specialists.

Sound healing reduces generalized anxiety during the pandemic: A feasibility study.

Objectives: This study examined the feasibility and effectiveness of a virtually-delivered, biofield-based sound healing treatment to reduce anxiety for individuals meeting criteria for Generalized Anxiety Disorder.

Design: This one-group, mixed-method feasibility study was conducted virtually via Zoom during the SARS-CoV-2 Pandemic. Fifteen participants with moderate to high levels of anxiety as determined by the Generalized Anxiety Disorder-7 (≥10), were enrolled.

Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity.

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties.

New isoxazolidinyl-based -alkylethanolamines as new activators of human brain carbonic anhydrases.

Carbonic anhydrases (CAs) are widespread metalloenzymes which catalyse the reversible hydration of carbon dioxide (CO) to bicarbonate (HCO) and a proton, relevant in many physiological processes. In the last few years, the involvement of CA activation in different metabolic pathways in the human brain addressed the research to the discovery of novel CA activators. Here, a new series of isoxazoline-based amino alcohols as CA activators was investigated.

Molecular interactions of PCSK9 with an inhibitory nanobody, CAP1 and HLA-C: Functional regulation of LDLR levels.

Objective: The liver-derived circulating PCSK9 enhances the degradation of the LDL receptor (LDLR) in endosomes/lysosomes. PCSK9 inhibition or silencing is presently used in clinics worldwide to reduce LDL-cholesterol, resulting in lower incidence of cardiovascular disease and possibly cancer/metastasis. The mechanism by which the PCSK9-LDLR complex is sorted to degradation compartments is not fully understood.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy.

Inorganic Drugs as a Tool for Protein Structure Solving and Studies on Conformational Changes.

Inorganic drugs are capable of tight interactions with proteins through coordination towards aminoacidic residues, and this feature is recognized as a key aspect for their pharmacological action. However, the "protein metalation process" is exploitable for solving the phase problem and structural resolution. In fact, the use of inorganic drugs bearing specific metal centers and ligands capable to drive the binding towards the desired portions of the protein target could represent a very intriguing and fruitful strategy.

Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold Repurposing Approach.

Intracellular pathogens, such as , have been recently shown to induce degradation of p53 during infection, thus impairing the protective response of the host cells. Therefore, p53 reactivation by disruption of the p53-MDM2 complex could reduce infection and restore pro-apoptotic effect of p53. Here, we report the identification of a novel MDM2 inhibitor with potential antitumoural and antibacterial activity able to reactivate p53.