PassaLab

Prof. Daniele Passarella’s Research Group
Department of Chemistry
University of Milan

Self-Assembled
Nanoparticles

Diversity-Oriented
Synthesis

Synthesis
of API

Natural Products
as Leads

PROTACs: Targeted Protein Degradation for Neurodegenerative and Cancer Targets

We are developing innovative PROTACs to degrade disease-related proteins implicated in neurodegenerative disorders (e.g. tau protein, DASPO) and cancers (tubulin). These bifunctional molecules hijack the ubiquitin-proteasome system to selectively remove otherwise undruggable targets.

Key publications: Pharmaceutics 2023, 15(5), 467; https://doi.org/10.3390/pharmaceutics15051467 BioRxiv 2025, https://www.biorxiv.org/content/10.1101/2025.05.22.655572v1

The project is coordinated by Prof. Passarella, member of the European research network ProteoCure – COST ACTION 20113.

Quantitative Live Cell Imaging of a Tauopathy model enables the Identification of a Polypharmacological Drug Candidate that Restores Physiological Microtubule Interaction

Nature Communications, 2024
A live-cell imaging of a tauopathy model enables screening of compounds that modulate taumicrotubule interaction and allows identification of a promising polypharmacological drug candidate that simultaneously inhibits tau aggregation and reduces tau phosphorylation. Find out more at the link.

A Green Approach to Nucleophilic Aromatic Substitutions of Nicotinic Esters in Cyrene

European Journal of Organic Chemistry, 2024
Cyrene has been used as an eco-friendly alternative to environmentally harmful polar aprotic solvents in SNAr reactions. This innovative protocol enabled the facile synthesis of a wide library of novel nicotinic esters, valuable precursors of bioactive compounds. This methodology could also be extended to scale-up processes, microwave-assisted synthesis, and one-pot telescoping reactions, thus enhancing its applicability in various eco-friendly synthetic contexts. Find out more at the link.

Sustainable Synthesis of 1,2,3-Triazoles using Cyrene as a Biodegradable Solvent in Click Chemistry

ChemSusChem, 2025
The first successful synthesis of 1,2,3-triazoles using Cyrene as a biodegradable and non-toxic solvent in click chemistry has been developed. Find out more here.

Synthesis of α-fluorocinnamate derivatives as novel cathepsin S inhibitors with in vitro antiproliferative activity against pancreatic cancer cells

Bioorg. Med. Chem., 2025
We have designed and synthesized three new derivatives basing on an isosteric replacement (H–F) at the level of cinnamate moiety. These derivatives emerged as potent covalent inhibitors of CatS (1.8–2.6 µM) with 2F showing also weak inhibition activity against CatL (20 %) and CatB (29 %). In vitro assays of 2F against pancreatic cancer cell lines BXPC3 and CAPAN1 revealed significant antiproliferative activity, with IC50 = 5.79 µM and 20.75 µM, respectively.. To find out more details follow the page

Biochemical Modulation of D-Asp Metabolism in Brain

Discovery of new small molecules inhibitors of hDASPO for the treatment of disorders connected to deficiency of D-Asp levels in brain. hDASPO inhibitors increases D-Asp in neuronal cells and thereby activates NMDA receptor function.

hDASPO project covers several multidisciplinary aspects, such as structural biology, synthetic organic chemistry and pharmacology, in collaboration with prof. Marco Nardini (Unimi) and Loredano Pollegioni (Uninsubria).

Nicotinic Acid Derivatives As Novel Noncompetitive α-Amylase and α-Glucosidase Inhibitors for Type 2 Diabetes Treatment

ACS Medicinal Chemistry Letters, 2024
A library of novel nicotinic acid derivatives, focusing on the modification of position 6 of the pyridine ring with (thio)ether functionalities, was mostly produced through an innovative green synthetic approach (Cyrene-based) and evaluated for their α-amylase and α-glucosidase inhibitory activity. Find out more under the Link

First Total Synthesis of Caerulomycin K: a Case Study on Selective, Multiple C–H Functionalizations of Pyridines

RSC Advances, 2024
Caerulomycins, natural alkaloids with antimicrobial properties, have been previously synthesized starting with highly pre-functionalized building blocks or requiring many functional group manipulations. In this work, we report the first total synthesis of caerulomycin K, a diversely trifunctionalized pyridine readily assembled in three steps exploiting the recent advancements in the C–H activation of N-heterocycles. Find out more under the Link

Metal-Free, Selective Ortho-Deuteration of N-Heterocyclic Oxides

Adv. Synth. Cat., 2025
In this work, we present a metal-free, selective ortho-deuteration of N-heterocycles starting from their N-oxides, proceeding at room temperature in just 5 minutes. More about it at this link

Design, synthesis and in vitro validation of bivalent binders of SARS-CoV-2 spike protein: Obeticholic, betulinic and glycyrrhetinic acids as building blocks

Bioorg. Med. Chem., 2025
Bivalent compounds have been designed to simultaneously bind both pockets of the Spike protein, offering significant advantages over single molecules or the combination of the two natural products. In vitro cell assays using pseudotyped recombinant lentiviral particles with selected SARS-CoV-2 Spike proteins demonstrated that 1 and 2 exhibit enhanced activity in reducing viral entry into target cells compared to individual natural products. Check it out at this link

Notice Board

Publications of the research group

Asymmetric Total Synthesis of (−)‐Glycybridin B, a Pharmacophore Screened Candidate for Tubulin Binding in Chemistry – A European Journal has the following publication status: Published Online

Chemistry – A European Journal 2025, DOI: 10.1002/chem.202502228

Alice Maiocchi, Maxim Shevelev, Zlata Boiarska, Juan Estévez-Gallego, Francesca Bonato, Paolo Orlando, Alessandra Chinosi, Emanuele Marcone, Andrea Citarella, Dragos Horvath, Michel O. Steinmetz, Andrea E. Prota, Alexandre Varnek, Valerio Fasano and Daniele Passarella

Synthesis and multitarget inhibitory effect of indole-based ethyl cinnamate derivatives against SARS-CoV-2 Mpro and cathepsins for broad-spectrum anti-coronavirus activity

Bioorganic and Medicinal Chemistry 2025, DOI: 10.1016/j.bmc.2025.118258

Andrea Citarella, Giulia Sibille, Davide Moi, Alessandro Dimasi, Tommaso Braga, Lorenzo Dal Col, Lorenzo Ruberto, Stefano Pieraccini, Maurizio Sironi, Nicola Micale, Tanja Schirmeister, Valerio Fasano, Alessandra Silvani, Clelia Giannini, Giorgio Gribaudo, Daniele Passarella

Design, synthesis and characterization of aryl bis-guanyl hydrazones as RNA binders of C9orf72 G4C2 extended repeats

European Journal of Medicinal Chemistry, 2025, 293, 117736, DOI: 10.1016/j.ejmech.2025.117736

Alice Maiocchi, Martina Pedrini, Veronica Ferrari, Agata Sofia Assunçao Carreira, Vincenzo Maria D’Amore, Federica Santoro, Anna Di Porzio, Maddalena Bosetti, Riccardo Cristofani, Alessandra Silvani, Diego Brancaccio, Luciana Marinelli, Francesco Saverio Di Leva, Alessandro Provenzani, Angelo Poletti, Pierfausto Seneci

News and save the date!

Upcoming webinars, seminars, conferences etc.

  • CDCO 2025 – Save the Date
    The 42nd National Conference of the SCI Organic Chemistry Division will take place in Villasimius (CA), 21–25 September 2025, at VOI Tanka Village.
    Official website →

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Professor Daniele Passarella

Full Professor of Organic Chemistry
University of Milan – Department of Chemistry

Email: daniele.passarella@unimi.it
Teaching

Curriculum Vitae