A5010730072- Computational Drug Discovery Methods
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Parkinson's Disease Mechanisms and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Microbial Natural Products and Biosynthesis
- Plant Gene Expression Analysis
- Sphingolipid Metabolism and Signaling
- Chemical Synthesis and Analysis
- Tryptophan and brain disorders
- Malaria Research and Control
- Protein Structure and Dynamics
- Neuropeptides and Animal Physiology
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Carbohydrate Chemistry and Synthesis
- Crystallization and Solubility Studies
- Quinazolinone synthesis and applications
- Synthesis and biological activity
- Biochemical and Molecular Research
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Histone Deacetylase Inhibitors Research
- Biochemical Acid Research Studies
- Microbial Metabolism and Applications
Aptuit (Italy)
2020-2025
University of Parma
2011-2021
Tools for molecular de novo design are actively sought incorporating sets of chemical rules fast and efficient identification structurally new chemotypes endowed with a desired set biological properties. In this paper, we present LiGen, suite programs which can be used sequentially or as stand-alone tools specific purposes. its standard application, LiGen modules to define input constraints, either structure-based, through active site identification, ligand-based, pharmacophore definition,...
Malaria eradication is a global health priority, but current therapies are not always suitable for providing radical cure. Artemisinin has paved the way malaria treatment, so-called Artemisinin-based Combination Therapy (ACT). However, with detection of resistance to ACT, innovative compounds active against multiple parasite species and at life stages needed. GlaxoSmithKline recently disclosed results phenotypic screening an internal library, publishing collection 400 antimalarial...
Pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase risk for developing Parkinson's disease a dominantly inherited fashion. These pathogenic variants, of which G2019S is most common, cause abnormally high activity, and compounds inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular processes, inhibitors can selectively target variant while sparing normal could offer...
Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA1–6). Among these, the role of LPA1 receptor in modulating fibrotic processes well-known, making it therapeutic target for pulmonary fibrosis and other disorders. Herein we report search new class antagonists oral treatment idiopathic with focus on hepatobiliary safety. Compound 7 excelled vitro vivo efficacy, showing significant efficacy both PD studies...
Cysteine is a building block for several biomolecules that are crucial living organisms. The last step of cysteine biosynthesis catalyzed by O-acetylserine sulfydrylase (OASS), highly conserved pyridoxal 5′-phosphate (PLP)-dependent enzyme, present in different isoforms bacteria, plants, and nematodes, but absent mammals. Beside the cysteine, OASS exerts series "moonlighting" activities such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, induction...
Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response infection via local tryptophan deprivation, active catabolite production, non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiology is...
On route toward a novel de novo design program, called LiGen, we developed docking LiGenDock, based on pharmacophore models of binding sites, including non-enumerative algorithm. In this paper, present the functionalities LiGenDock and its accompanying module LiGenPocket, aimed at site analysis structure-based definition. We also report optimization procedure have carried out to improve cognate virtual screening performance LiGenDock. particular, applied experiments (DoE) methodology screen...
d-Serine is the co-agonist of NMDA receptors and binds to so-called glycine site. synthesized by human serine racemase (SR). Over activation involved in many neurodegenerative diseases and, therefore, inhibition SR might represent a novel strategy for treatment these pathologies. very difficult target, with only few compounds so far identified exhibiting weak inhibitory activity. This study was aimed at identification inhibitor mimicking malonic acid, best-known inhibitor, cyclopropane...
3-Hydroxyanthranilic acid 3,4-dioxygenase (3-HAO) is the enzyme responsible for production of neurotoxic tryptophan metabolite quinolinic (QUIN). Elevated brain levels QUIN are observed in several neurodegenerative diseases, but pharmacological investigation on its role pathogenesis these conditions difficult because only one class substrate-analogue 3-HAO inhibitors, with poor chemical stability, has been reported so far. Here we describe design, synthesis, and biological evaluation a novel...
Background: G-protein coupled receptors may exist as functional homodimers, heterodimers and even higher aggregates. In this work, we investigate the 5-HT2A receptor, which is a known target for antipsychotic drugs. Recently, has been shown to form homodimers with mGluR2 receptor. The objective of study build up 3D models 5-HT2A/mGluR2 heterodimer 5-HT2A-5-HT2A homodimer, evaluate impact dimerization interface on shape binding pocket by using molecular dynamics simulations docking studies....
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by lung leading to an irreversible decline of function. Current antifibrotic drugs on the market slow down but do not prevent progression are associated with tolerability issues. The involvement lysophosphatidic acid receptor 2 (LPA2) in IPF supported LPA2 knockdown studies. To further validate role receptors modulating potentially other fibrotic processes, potent selective antagonist good pharmacokinetic...