Research Research topics

Research topics

Design, synthesis, and study of molecules of pharmacological interest to identify structure-activity relationships aimed at optimizing interaction with biological macromolecules in terms of both activity and selectivity.

Prof. Maria Novella Romanelli, Prof. Elisabetta Teodori, Prof. Dina Manetti

In particular, the research focuses on the study of:

• molecules capable of reversing pharmacoresistance in cancer cells through inhibition of efflux pumps responsible for cross-resistance to chemotherapeutics (multidrug resistance (MDR)) and the carbonic anhydrase isoform XII. These proteins are co-overexpressed on the cell membrane of certain chemoresistant tumor cells.
• molecules able to combat infections by multi-resistant Gram-negative bacteria, acting as inhibitors of RND efflux pumps that increase drug efflux to the extracellular environment, inhibitors of metallo-beta-lactamase enzymes that inactivate beta-lactam antibiotics, or inhibitors of biofilm formation associated with persistent infections.
• molecules capable of inhibiting HCN channels, proteins activated by hyperpolarization that regulate neuronal and cardiac electrical activity. Selective inhibitors for specific isoforms can be used in neuropathic pain, epilepsy, arrhythmias, and angina.
• molecules capable of selectively modulating one or more carbonic anhydrase isoforms. Selective inhibitors can be tested in models of pain, glaucoma, and cancer. Activators can be used as tools to understand the pathophysiological role of less-studied isoforms.

Design and synthesis of small molecules as pharmacological tools and potential therapeutic agents

Prof. Vittoria Colotta, Prof. Daniela Catarzi, Prof. Flavia Varano

The research activity of the pharmaceutical chemistry team focuses on the synthesis and structural characterization of new small molecules designed to interact with specific proteins involved in high-impact diseases, aiming to identify novel therapeutic approaches. Particular attention is given to the development of adenosine receptor ligands, carbonic anhydrase modulators, casein kinase 1δ and CD73 inhibitors, which represent potential new therapeutic agents for cancer and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Part of the research is devoted to the design and synthesis of multitarget molecules to explore their potential as innovative polypharmacological agents for the treatment of multifactorial diseases. The interdisciplinary approach drives the team’s activities, which are closely coordinated with other research groups handling the biological and pharmacological characterization of target compounds and their in silico structural optimization. The team also explores green strategies for the synthesis and purification of the compounds under investigation.

Rational design and synthesis of biologically active molecules

Prof. Claudiu T. Supuran, Prof. Paola Gratteri, Dr. Alessio Nocentini, Dr. Alessandro Bonardi

The group’s research focuses primarily on:

Prof. P. Gratteri: development and application of computational chemistry, bioinformatics, and molecular graphics tools applied to rational drug design and lead identification. The computational approaches mainly used are structure-based and ligand-based, including ▪ molecular docking, ▪ molecular dynamics simulations, ▪ statistical mechanics methods for analyzing the thermodynamics of ligand-receptor complex formation, ▪ ADMET property prediction, ▪ QM/MM mixed methods, ▪ multivariate analysis techniques.

Main targets of interest: ▪ DNA, in both its double helix (ds) and non-canonical G-quadruplex forms; ▪ carbonic anhydrases, both human and bacterial; ▪ ion channels; G-protein coupled receptors.

Prof. Gratteri has authored numerous publications in high-impact national journals (PubMed; Scopus), as well as numerous conference contributions and book chapters.

Prof. C.T. Supuran: enzyme inhibitors/activators; carbonic anhydrases; matrix metalloproteases and bacterial zinc proteases; cysteine proteases (SARS-CoV-2 and related proteins); tyrosinase; epoxide hydrolases; cyclooxygenases; anti-glaucoma, anti-obesity, anticancer drugs; anti-infective agents for pathogens resistant to classical therapies (antibacterial, antifungal, antiprotozoal); neuropathic pain agents.

Main targets of interest: ▪ human and non-human carbonic anhydrases; ▪ ion channels; G-protein coupled receptors; ▪ proteases.

Prof. Supuran has authored numerous publications in high-impact journals (PubMed; Scopus) and a significant number of conference contributions and book chapters.

Drug design and development of new enzyme modulators

Prof. Fabrizio Carta

The scientific activities are focused on Pharmaceutical and Nutraceutical Chemistry, specifically on disciplines related to Drug Discovery and Development (DDD). Studies include: in silico design, multi-step organic and/or organometallic synthesis, physicochemical characterization, and in vitro kinetic profiling of compounds with potential human and/or veterinary pharmaceutical-nutraceutical applications. Structural characterization and activity studies are conducted on medically relevant enzymes involved in inflammatory, tumor, neurodegenerative, and infectious diseases.

PeptLab – Interdepartmental Research Unit on Peptide and Protein Chemistry and Biology

Prof. Paolo Rovero

PeptLab is a multidisciplinary research unit with strong expertise in peptide science (design, synthesis, and molecular characterization, both biologically and structurally). Current projects, detailed on the lab homepage (www.peptlab.unifi.it), include:

• Bioactive peptides for pharmaceutical and cosmeceutical applications.
• Innovative methods for peptide synthesis and modification.
• Peptides and sustainability: new approaches and applications to reduce health impact.
• Peptide-based diagnostics for immune-mediated diseases.
• Surface plasmon resonance for label-free analysis of biomolecular interactions.

Food Chemistry

Prof. Nadia Mulinacci, Prof. Marzia Innocenti, Dr. Maria Bellumori

The group focuses on developing extraction methods for determining bioactive secondary metabolites primarily from various parts (fruits, leaves, flowers, seeds, bark, tubers, etc.) of edible plants, medicinal plants, and agro-food by-products. Activities include chromatographic techniques (HPLC coupled with UV-Vis or DAD detectors) and combined MS (HPLC/API MS, MS/MS) and NMR analyses for structural characterization of natural compounds in plant extracts. A key activity is developing multi-target chromatographic methods for quality control of plant extracts for food use, mainly containing phenolic compounds, alkaloids, and saponins.

• Studies defining chemical composition and bioactivity of secondary metabolites from Olea europaea L., including phenolic compounds in fruits, leaves, OEVO, by-products of crushing, and volatile compound profiles of virgin olive oils (HS-SPME-GC-MS).
• Studies on starch and resistant starch, phenols, and ferulates in minor cereals (e.g., millet).
• Studies on coffee as a beverage and by-products for alkaloid and chlorogenic acid content.
• Studies on chemical composition and bioactivity of pomegranate extracts (juice, peel, and fermented peel).
• Extraction and analysis of natural polysaccharides (pomegranate, algae, date extracts) and evaluation of their prebiotic properties.
• Production of phytochemically characterized plant extracts for in vitro and in vivo biological testing.

Pharmaceutical Technology

Prof. Anna Rita Bilia, Prof. Maria Camilla Bergonzi, Prof. Francesca Maestrelli

Research focuses on design, development, physicochemical characterization, and biopharmaceutical evaluation of modern therapeutic systems. Drug and natural product bioavailability and technological properties are enhanced through conventional and innovative drug delivery systems. Micro- and nanoformulations (liposomes, vesicles, micelles, nanoparticles, micro- and nanoemulsions, lipid carriers, inclusion complexes, solid dispersions) are designed and characterized using HPLC-DAD, HPLC-MS, DLS, ELS, TEM, SEM, DSC, solubility and dissolution studies. Stability is tested under various conditions and media, and in vitro permeability (PAMPA) is applied using artificial membranes mimicking physiological barriers. Caco-2 and hCMEC/D3 cells are used as intestinal and blood-brain barrier models.

 

Advanced Applications in Mass Spectrometry (MS) for the Development of Analytical Methods to Study Biologically and Pharmacologically Relevant Molecules

Prof. Gianluca Bartolucci

The potential of MS techniques in pharmaceutical and biomedical research is well documented. The high specificity, selectivity, and sensitivity of mass spectrometry coupled with chromatography (GC-MS or HPLC-MS) allows the study of compounds individually or in mixtures, as well as in complex matrices. In recent decades, MS has been employed as a selected analytical method for various investigations, such as drug stability in different matrices (buffers, plasma, etc.), evaluation of potential biomarkers for disease characterization, or determination of a compound’s concentration (analyte) in biological media. Prof. Gianluca Bartolucci’s laboratory supports other research groups in identifying new biological targets, quantitatively determining analytes of interest, and characterizing chemical structures. The lab is equipped with various mass spectrometers covering both volatile compound analysis (GC-MS) and polar compound analysis (HPLC-MS). Instruments also allow complex MS experiments, tandem mass spectrometry (MS/MS and MS^n), and high-resolution mass measurements (HRMS).

Application of Modern Analytical and Chemometric Techniques for Pharmaceutical Research and Development

Prof. Sandra Furlanetto, Dr. Serena Orlandini

Quality by Design (QbD) and Analytical Quality by Design (AQbD). QbD is an approach used to ensure process or product quality and is applicable across manufacturing sectors. In pharmaceuticals, it is incorporated in ICH guidelines. Recent guidelines ICH 14 and ICH Q2(R2) consider AQbD central to analytical method development, integrating optimization and validation to produce high-quality data while optimizing costs and environmental impact. QbD and AQbD use multivariate and risk-management approaches.

Quality Control: ensures the quality of finished products (biopharmaceutical, pharmaceutical, food, nutraceutical, cosmetic, etc.) and requires deep knowledge of regulations and analytical data handling. In biopharmaceuticals, the presence of biosimilars requires analytical platforms to determine Critical Quality Attributes (CQA) ensuring product safety and efficacy. In pharmaceuticals, the challenge is simultaneously detecting the active ingredient in large quantities and possible impurities present in much lower concentrations. HPLC is the most used separation technique, with capillary electrophoresis also recognized as a green alternative.

Optimization through experimental design strategies: Experimental design allows exploring the optimal conditions for a system within a defined experimental space. Unlike outdated univariate approaches, multivariate design evaluates variable interactions and identifies optimal regions. It can be applied whenever a process influenced by multiple variables is studied.

Integrated use of analytical and chemometric methods for classification and information extraction. Data extraction highlights similarities, identifies product origins, potential quality markers, provenance, or storage conditions.

Study of separation mechanisms in analytical systems through integrated molecular modeling, NMR, and separation parameter studies.

Cardiovascular Pharmacology

Prof. Elisabetta Cerbai, Prof. Laura Sartiani, Dr. Raffaele Coppini

Research focuses on the pathophysiological mechanisms of cardiomyopathies, identification of new therapeutic targets, and preclinical development of pharmacologically active substances. Studied cardiomyopathies include acquired and congenital types, with particular focus on atrial, ventricular, or conduction system excitation-contraction alterations. Experiments employ ex vivo models (human atrial and ventricular tissue fragments or rodent/zebrafish models), in vivo rodent and zebrafish models, and in vitro cardiomyocyte and organoid cultures from rodents or human pluripotent stem cells. This multi-level approach provides an integrated view of cardiac functional complexity, from single cells to tissue and organoid, where cellular phenotypes organize to mimic native tissue. Active compounds, synthetic or nutraceutical, are tested for modulation of excitation-contraction functions via multiple molecular targets, including ion channels, pumps, exchangers, receptor complexes, and transcription factors. Techniques include electrophysiology, optogenetics, live-cell fluorescence imaging, gene/protein expression analysis, immunohistochemistry, and genetic editing using plasmid and viral vectors.

Antitumor Pharmacology

Dr. Stefania Nobili

Research focuses on cytotoxic activity of new compounds with potential anticancer effects and molecular mechanisms of sensitivity/resistance to anticancer drugs in preclinical tumor models. Translational studies in pharmacogenetics and pharmacogenomics aim to identify molecular determinants responsible for tumor drug resistance or toxicity in major solid and hematological cancers. These determinants serve as predictive biomarkers of response, potential drug targets, or modulatory sites for enhancing anticancer drug activity, forming a basis for more effective personalized therapies. Studies use human tumor cell lines (sensitive or resistant), tumor explants, biological fluids, and derived in vitro cellular models.

Neuroinflammation and Cellular Senescence

Prof. Nicoletta Galeotti

Research focuses on mechanisms underlying neuroinflammation and cellular senescence in neurodegenerative diseases associated with neuropathic pain, identifying new pathophysiological mechanisms and potential targets for preclinical development of innovative therapies. In vitro studies use glial and neuronal cell lines to reproduce etiological causes of major neuropathies. In vivo studies employ animal models of central and peripheral neuropathic conditions, such as multiple sclerosis and diabetic, alcoholic, or trauma-induced neuropathies. Analysis of nervous tissue samples allows investigation of neuroinflammation, cellular senescence, and accumulation of senescent cells during disease onset and progression. Therapeutic development involves modulation of intracellular pathways in microglia (RNA-binding proteins, CB2 and TREM receptors, epigenetic modulators) and nociception at central and peripheral levels. Potential treatments include natural compounds, new synthetic molecules, and precision medicine strategies such as antisense therapy.

Pain Pharmacology

Prof. Carla Ghelardini, Prof. Lorenzo Di Cesare Mannelli

Research addresses pathophysiological mechanisms of pain, identification of new therapeutic targets, and preclinical development of pharmacologically active substances. Persistent somatic and visceral pain is analyzed for nociceptive, inflammatory, neuropathic, and nociplastic components. In vitro studies use neuronal and glial cell lines, spinal cord organotypic cultures, and organoids. Development of non-animal models includes colon epithelial organoids for visceral hypersensitivity studies and dorsal root ganglia organoids derived from human induced pluripotent stem cells for peripheral neuropathy studies. In vivo studies focus on osteoarthritis, rheumatoid arthritis, trauma- and chemotherapy-induced neuropathies, and chronic intestinal diseases. Therapeutic approaches involve modulation of molecular pain mediators (e.g., VEGF-A receptor 1, pannexin 1 channel), regulatory systems (e.g., glymphatic system), or symbiotic relationships (e.g., gut microbiota via fecal transplant). Tested compounds include synthetic small molecules, biotechnological products, and natural substances from terrestrial and marine organisms.

Experimental and Translational Toxicology

Prof. Cristina Luceri, Prof. Lisa Giovannelli, Dr. Elisabetta Bigagli

Clinical research focuses on risk factors associated with chronic-degenerative diseases, including tumors, metabolic disorders, and gastrointestinal diseases.

• Identification of biomarkers of susceptibility and therapeutic response
• Identification of new biochemical and epigenetic markers, both tissue and circulating, as indicators of disease and/or predictors of therapeutic response or adverse drug reactions in adults and pediatric patients
• Identification of biochemical, genetic, and epigenetic biomarkers predictive of health risk, particularly for tumors associated with lifestyle, diet, or occupational toxic exposure in healthy volunteers and exposed workers

Research projects are multidisciplinary, carried out in collaboration with clinicians (Gynecology, Gastroenterology, Abdominal Surgery, ENT, Diabetology, Clinical Nutrition at Careggi and Meyer hospitals). Biological samples are analyzed using omics techniques (miRNA, transcriptome), DNA damage assays, protein analysis, and other markers to evaluate oxidative stress or inflammation.

• Evaluation of the safety profile of drugs in non-profit clinical trials

Research includes collection, assessment, and monitoring of adverse events, interaction with Regulatory Authorities and Ethics Committees, and continuous reassessment of the risk-benefit profile (responsibility for pharmacovigilance and EMA authorization for SUSAR reporting and XEVMPD database use).

Preclinical research: pharmacotoxicological evaluation of synthetic molecules and natural extracts regarding cellular toxicity, intestinal absorption according to EMA/ICH M9 guidelines, gastro-protective activity, modulation of inflammation, oxidative stress, and mechanism of action. Projects are conducted on cellular models such as Caco-2 on transwells, reconstructed Episkin epithelia, human keratinocytes, human dermal fibroblasts, murine macrophages, and tumor cell lines.

Pharmacovigilance and Pharmacoepidemiology

Prof. Alfredo Vannacci, Dr. Niccolò Lombardi, Dr. Giada Crescioli, Eng. Roberto Bonaiuti

Research uses an observational analytical approach aimed at acquiring comprehensive scientific and clinical information on the benefit/risk profile of drugs, vaccines, and integrative medicine products used in real-world settings. Leveraging multidisciplinary expertise, advanced equipment, and facilities, research covers pre- and post-marketing pharmacological surveillance: evaluation of pharmacodynamic and pharmacokinetic mechanisms in adverse drug/vaccine reactions (pharmacovigilance and vaccinovigilance); safety assessment in populations including vulnerable groups (<18 and ≥65 years), special conditions (pregnancy, breastfeeding, addiction), and high-risk environments (emergency, clinical toxicology); assessment of integrative medicine products (herbovigilance and clinical phytotherapy); evaluation of prescribing appropriateness and drug utilization in clinical practice.

Technological solutions for pharmacology and pharmacovigilance: Scarab Joint Laboratory (Neurofarba Dept., Dynamedics, Spindox) develops IT applications in healthcare, specializing in pharmacology, pharmacovigilance, and pharmacoepidemiology.

Perinatal pharmacology research: the PeaRL Perinatal Research Laboratory (Neurofarba Dept. & CiaoLapo Foundation ETS) conducts basic, preclinical, epidemiological, and clinical research on perinatal mental and physical health. Main focuses include: safe drug use during pregnancy and postpartum, management of misuse, abuse or dependence, effects of environmental factors, pollutants, lifestyle, and life events on maternal and couple wellbeing, and child neurodevelopment from preconception through the first 1,000 days of life.

Pediatric Rheumatology

Prof. Gabriele Simonini

Research focuses on chronic inflammatory diseases in pediatric populations. Key areas include juvenile idiopathic arthritis, Kawasaki disease, uveitis, pediatric connective tissue diseases, and autoinflammatory syndromes.

Current projects include:

• Kawasaki Syndrome: identification of pathogenetic inflammatory mechanisms and coronary involvement biomarkers
• Autoinflammatory Syndromes: genotype-phenotype correlation and disease severity risk stratification
• Chronic Pediatric Inflammatory Uveitis: clinical, biochemical, genetic, and tear markers predicting response to biological therapy
• Pediatric Connective Tissue Diseases: identification of predictors of disease outcome
• Pediatric Scleroderma Syndromes: outcome assessment and therapy response
• Behçet Syndrome: transcriptomic and genomic cohort analysis for adult-phenotype comparison
• Therapy with biologically active modulatory drugs: identification of anti-drug autoantibodies and clinical correlation of efficacy
• Active collaborations with international research centers and societies:

Paediatric Rheumatology International Trials Organisation (PRINTO)

Childhood Arthritis and Rheumatology Research Alliance (CARRA)

Pediatric Rheumatology European Society (PReS)