In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents

Gennaio 10th, 2023|

Abstract Different molecular mechanisms contribute to the development of multidrug resistance in cancer, including increased drug efflux, enhanced cellular repair mechanisms and alterations of drug metabolism or drug targets. ABCG2 is a member of the ATP-binding cassette superfamily transporters that [...]

Editorial: Novel Strategies in Drug Development Against Multifactorial Diseases

Dicembre 21st, 2022|

Editorial on the Research Topic Novel Strategies in Drug Development Against Multifactorial Diseases The complexity of multifactorial diseases, such as inflammation, cancer, neurodegenerative disorders, infectious pathologies represents a key obstacle in the success of therapeutic intervention. The occurrence of acquired [...]

Discovery and Optimization of Indoline-Based Compounds as Dual 5-LOX/sEH Inhibitors: In Vitro and In Vivo Anti-Inflammatory Characterization

Novembre 26th, 2022|

Abstract The design of multitarget drugs represents a promising strategy in medicinal chemistry and seems particularly suitable for the discovery of anti-inflammatory drugs. Here, we describe the identification of an indoline-based compound inhibiting both 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase [...]

Extensive Molecular Dynamics Simulations Disclosed the Stability of mPGES-1 Enzyme and the Structural Role of Glutathione (GSH) Cofactor

Novembre 16th, 2022|

Abstract A deep in silico investigation of various microsomal prostaglandin E2 synthase-1 (mPGES-1) protein systems is here reported using molecular dynamics (MD) simulations. Firstly, eight different proteins models (Models A−H) were built, starting from the active enzyme trimer system (Model A), [...]

Identification of 2,4-Dinitro-Biphenyl-Based Compounds as MAPEG Inhibitors

Novembre 16th, 2022|

Abstract Multipronged strategy: 2,4-Dinitro-biphenyl-based compounds were identified as inhibitors of leukotriene C4 synthase (LTC4S) and 5-lipoxygenase-activating protein (FLAP), both members of the “Membrane Associated Proteins in Eicosanoid and Glutathione metabolism” (MAPEG) family involved in the biosynthesis of pro-inflammatory eicosanoids. The results [...]

Indocyanine Green Endoscopy for Pituitary Adenomas with Parasellar Extension: Results from a Preliminary Case Series

Settembre 9th, 2022|

Abstract Background Advances in visualization tools have brought new confidence, including endoscope-integrated indocyanine (E-ICG), which makes pituitary and skull-base surgery safer and more effective. We report here our preliminary experience with the use of E-ICG to 1) visualize the cavernous segment of [...]

“Sagittal Crest”: Definition, Stepwise Dissection, and Clinical Implications From a Transorbital Perspective

Maggio 20th, 2022|

Abstract BACKGROUND:  The recent development of the superior eyelid endoscopic transorbital approach (SETOA) offered a new route for the management of cavernous sinus and middle cranial fossa tumors. As a result, a constant anatomic landmark of the surgical pathway after drilling the medial edge of the greater sphenoid wing (GSW) [...]

Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series

Marzo 23rd, 2022|

Abstract OBJECTIVES:  A recent study suggests that Multisystem Inflammatory Syndrome in Children (MIS-C) is triggered by gastrointestinal breach of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral particles from the gut lumen into systemic circulation. The virus remains in the [...]

Optimization of Peripheral Blood Mononuclear Cell Extraction from Small Volume of Blood Samples: Potential Implications for Children-Related Diseases

Febbraio 24th, 2022|

Abstract Managing medical procedures for children with problematic disorders is a challenging approach, especially in the case of blood withdrawal for autism spectrum disorder-affected children. Peripheral blood mononuclear cells (PBMC) represent an important cellular model to study immune responses and [...]

Identification of a dual acting SARS-CoV-2 proteases inhibitor through in silico design and step-by-step biological characterization

Ottobre 22nd, 2021|

Abstract COVID-19 pandemic, starting from the latest 2019, and caused by SARS-CoV-2 pathogen, led to the hardest health-socio-economic disaster in the last century. Despite the tremendous scientific efforts, mainly focused on the development of vaccines, identification of potent and efficient [...]

Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation

Agosto 30th, 2021|

Abstract A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (Mpro), [...]

Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition

Maggio 7th, 2021|

We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the [...]