Drug Design and Synthesis Center (CHIM/08)

Attività di ricerca

The Drug Design and Synthesis Center (DDSC) research activity is focused on the achievement of new chemical entities in the areas of antiviral, anticancer and CNS agents to develop new potential drugs.
1- Development on Anticancer Agents: the strategy of inducing cell death through an interference with the dynamics of microtubules has proved to be successful in the design of effective antitumor drugs. Aim of this project is the design and synthesis of new microtubule targeting agents as inhibitors of tubulin polymerization to develop drug candidate for cancer treatment, including breast cancer, glioblastoma and leukemia.
2- Novel Antiviral Agents: the overall goal is to design novel inhibitors for different viruses and to develop them into potent lead candidates for antiviral therapy. Current research projects are focused on HIV-1, Norovirus, Dengue, and Zika viruses.
3- Novel CNS Agents: this research project has been focused on the development of highly effective CNS agents as monoamine oxidase inhibitors and CB1endocannabinoid receptor ligands.
4- DDSC Computational Drug Design Platform: DDSC can support a wide variety of drug discovery research projects by means of modern computational methodologies to guide the hit-to-lead optimization process and to develop them into drug candidates.
5- Microwave-assisted synthesis: The work is focused on the development of new procedures for microwave-assisted synthesis of heterocyclic compounds of pharmaceutical interest.

Collaborazioni nazionali e internazionali

Anticancer agents:

  • Ernest Hamel, National Cancer Institute, National Institutes of Health, Frederick, USA;
  • Andrea Brancale,Cardiff University, Cardiff, UK;
  • Carmela Mazzoccoli, IRCCS, C. di Riferimento Oncologico della Basilicata, Rionero in V., It;
  • Patrizia Lavia, Istituto di Biologia Molecolare del CNR, Roma, It;
  • Daniel Merk, Goethe-University, Frankfurt, De.

Antiviral agents:

  • José A. Esté, IrsiCaixa, Universitat Autonóma de Barcelona, Badalona, Es;
  • Giovanni Maga, Istituto di Genetica Molecolare, CNR, Pavia, It;
  • Johan Neyts, KU Leuven, Be;
  • Jin-Ching Lee, Kaohsiung Medical University, Taiwan, Tw;
  • Eloise Mastrangelo, CNR-IBF, Milano, It;
  • Daniele Castagnolo, King's College, London, UK.

Endocannabinoid ligands:

  • Vincenzo di Marzo, Istituto di Chimica Biomolecolare, CNR, Pozzuoli, It;
  • Giancarlo Colombo, Istituto di Neuroscienza, CNR, Cagliari, It.

Synthetic unit:

  • CEM Discover SP single-mode reactor equipped with an Explorer 72 autosampler
  • PerkinElmer Spectrum 100 FT-IR spectrophotometer equipped with ATR accessory
  • NMR Bruker Avance (400 MHz) spectrometer equipped with 12-position autosampler
  • Thermo Fisher Scientific Inc. Dionex UltiMate 3000 HPLC system.

Computational unit:

  • Schrodinger suite;
  • GOLD, PLANTS and Autodock (docking);
  • AMBER, Gromacs (Molecular Dynamics);
  • LeadIt (core hopping and rebranching);
  • MolInspiration (ADME prediction).
Settori ERC
  • Pharmacology, pharmacogenomics, drug discovery and design, drug therapy (LS7_3)
  • Organic chemistry (PE5_17)
  • Cardiovascular diseases (LS4_7)
  • Food sciences (including food technology, nutrition) (LS9_5)
  • Cancer and its biological basis (LS4_6)


22-03-2010 - 22-09-2012 (30 months), Drug design, synthesis and biological evaluation of antitumor agents targeting mitosis, PRIN, Italian MIUR, Principal Investigator

01-02-2013 - 01-02-2016 (36 months) Drug design, synthesis and biological studies of innovative drugs againts cancer. PRIN, Italian MIUR, Principal Investigator
05-02-2017 - 05-02-2020 (36 months) New perspectives treatment to treat glioblastoma multiforme trhogh a multitarget approach, PRIN, Italian MIUR, Principal Investigator
2009-2011 (36 months), Drug design and synthesis of non-nucleoside inhibitors of both HIV-1 wild type and resistant mutant strains reverse transcriptase, and coxsackie B4 virus, Istitute Pasteur Italy, Principal Investigator
2012 - 2015 (36 months), New non-nucleoside antiviral agents targeting HIV-1 reverse transcriptase . Istitute Pasteur Italy, Principal Investigator
23-06-2011 - 23-06-2015, (48 months), The molecular basis of the diseases, FIRB, Italian, Research Unit Coordinator
01-12-2014 - 31-12-2015, (13 months), Design and synthesis of a series of N-(piperidin-4-ylmethyl)-1H-indazole-3-carboxamide derivatives, A.C.R.A.F. SpA, Italy, Principal Investigator
01-04-2016 - 01-02-2017 (10 months), Synthesis of a series of tetrahydro-1H-pyrazolopyridine and imidazopyridine derivatives, A.C.R.A.F. SpA, Italy, Principal Investigator
22-06-2012 - 29-03-2013 - 13-12-2013 (24 months) Synthesis of scaffolds useful for targeted chemical libraries, European Institute of Oncology, Italy, Principal Investigator

Publication 2018-2020 (July, 21)

  1. Mollica, A.; Macedonio, M.; Stefanucci, A.; Costante, R.; Carradori, S.; Cataldi, V.; Di Giulio, M.; Cellini, L.; Silvestri, R.; Giordano, C; Scipioni, A.; Morosetti, S.; Punzi, P.; Mirzaie, S. Arginine- and Lysine-rich peptides: Synthesis, characterization and antimicrobial activity. Lett. Drug Des. Disc. 2018, 15, 220-226. (doi: 10.2174/1570180814666170213161341; IF 2018: 0.924).
  2. Simona Daniele, Deborah Pietrobono, Barbara Costa, Mariateresa Giustiniano, Valeria La Pietra, Chiara Giacomelli, Giuseppe La Regina, Romano Silvestri,3 Maria Letizia Trincavelli, Ettore Novellino, Claudia Martini, Luciana Marinelli. Bax activation blocls self-renewal and induces apoptotis of human glioblastoma stem cells. ACS Chem. Neurosci. ACS Chem. Neurosci. 2018, 9, 85-99. (doi: 10.1021/acschemneuro.7b00023, IF 2016: 3883).
  3. Valeria Famiglini and Romano Silvestri. Indolylarylsulfones, a fascinating story of highly potent HIV type-1 non-nucleoside reverse transcriptase inhibitors. Antiviral Chem. and Chemoth. 2018, 26, 1-19. IF 2018 not yet available. AVCC is published by SAGE since 2017).
  4. Filipović, Nenad; Bjelogrlić, Snežana; Pelliccia, Sveva; Jovanović, Vesna ; Kojić, Milan; Senćanski, Milan; La Regina, Giuseppe; Silvestri, Romano; Muller, Christian; Todorović, Tamara. Selenotriapine – An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors Arabian J. Chem. 2017, in press. (doi: 10.1016/j.arabjc.2017.11.017; 5-year IF 4.0).
  5. Riccio, Gennaro; Bottone, Sara; La Regina, Giuseppe; Badolati, Nadia; Passacantilli, Sara; Rossi, Giovanni; Accardo, Antonella; Dentice, Monica; Silvestri, Romano; Novellino, Ettore; Stornaiuolo, Mariano. A negative allosteric modulator of the WNT receptor Frizzled 4 switches into an allosteric. Biochemistry 2018, 57, 839-851. (doi: 10.1021/acs.biochem.7b01087, IF 2017 2.997).
  6. Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Luca Mologni, Daniele Vergar, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Daniela Bonetti, Candice Gautier, Stefano Gianni, Romano Silvestri, Valeria Famiglini, Valentina Naccarato, Carlo Gambacorti Passerini, Michele Maffia, Addolorata M.L. Coluccia. β-Catenin knockdown promotes NHERF1-mediated survival of colorectal cancer cells: implications for a double-targeted therapy. Oncogene 2018, 37, 3301-3316. (doi: org/10.1038/s41388-018-0170-y, 5-year IF 6.993).
  7. F. Ricci,  L. Carrassa, M. S. Christodoulou, D. Passarella, B. Michel, R. Benhida, N. Martinet, A. Hunyadi, E. Ioannou, V. Roussis, L. Musso, S. Dallavalle, R. Silvestri, N. Westwood, M. Mori, C. Ingallina, B. Botta, E. Kavetsou, A. Detsi, Z. Majer, F. Hudecz, S. Bosze, B. Kaminska, T.V. Hansen, P. Bertrand, C. M. Athanassopoulos, G. Damia. A high-throughput screening of a chemical compound library in ovarian cancer stem cells. Combinatorial Chemistry & High Throughput Screening 2018, 21, 50-56 (doi: 10.2174/1386207321666180124093406, IF 2017 1.205).
  8. [154] R. Carnevale, R. Silvestri, L. Loffred, M. Novo, V. Cammisotto, V. Castellani, S. Bartimoccia, F. Violi. Oleuropein, a component of extra virgin olive oil, lowers post-prandial glycaemia in healthy subjects. British Journal of Clinical Pharmacology 2018, 84, 1566-1574. (doi:10.1111/bcp.13589, IF 2018: 3.838).
  9. G. La Regina, R. Bai, A. Coluccia, V. Naccarato, V. Famiglini, M. Nalli, D. Masci, A. Verrico, P. Rovella, C. Mazzoccoli, E. Da Pozzo, C. Cavallini, C. Martini, S. Vultaggio, G. Dondio, M. Varasi, C. Mercurio, E. Hamel, P. Lavia, R. Silvestri. New 6- and 7-heterocyclyl-1H-indole derivatives as potent tubulin assembly and cancer cell growth inhibitors with potential to treat human liver carcinoma and glioblastoma. Eur. J. Med. Chem. 2018, 152, 283-297. (doi: 10.1016/j.ejmech.2018.04.042, IF 2018; IF 2017: 4.816).
  10. Laurène Da Costa, Els Scheers, Antonio Coluccia, Adriano Casulli, Manon Roche, Carole Di Giorgio, Johan Neyts, Thierry Terme, Roberto Cirilli, Giuseppe La Regina, Romano Silvestri, Carmen Mirabelli, Patrice Vanelle. Structure-based drug design of potent pyrazolic derivatives against Rhinovirus replication. J. Med. Chem. 2018, 27, 8402-8416. (doi: 10.1021/acs.jmedchem.8b00931; IF 2018: 6.253).
  11. Antonio Coluccia, Giuseppe La Regina, Valentina Naccarato, Marianna Nalli, Viviana Orlando, Stefano Biagioni, Maria Laura De Angelis, Marta Baiocchi, Candice Gautier, Stefano Gianni, Fiorella Di Pastena, Laura Di Magno, Gianluca Canettieri, Addolorata Maria Luce Coluccia, Romano Silvestri. Drug Design and Synthesis of First in Class PDZ1 targeting NHERF1 Inhibitors as Anticancer Agents. ACS Med. Chem. Lett. 2019, 10, 499-503. article ASAP: doi: 10.1021/acsmedchemlett.8b00532; IF 2018: 3.794)
  12. Giuseppe La Regina, Antonio Coluccia, Valentina Naccarato, Romano Silvestri. New anti-cancer agents through an interaction with tubulin. European Journal of Pharmaceutical Sciences 2019, 131, 58-68. doi: 10.1021/acsmedchemlett.8b00532.
  13. Vittoria Cammisotto, Roberto Carnevale, Cristina Nocella, Lucia Stefanini, Simona Bartimoccia, Pasquale Pignatelli, Daniele Pastori, Antonio Coluccia, Romano Silvestri and Francesco Violi Nox2-mediated platelet activation by glycoprotein (GP) VI: effect of rivaroxaban alone and in combination with aspirin. Biochem. Pharmacol 2019, 163, 111-118. (doi: 10.1016/j.bcp.2019.02.016, IF 2018: 4.235).
  14. Marion Laudette, Antonio Coluccia, Yannis Sainte-Marie, Andrea Solari, Loubina Fazal, Pierre Sicard, Romano Silvestri, Sandrine Pons, Bijan Ghaleh, Jean-Paul Blondeau, Frank Lezoualc’h. Identification of a pharmacological inhibitor of Epac1 that protects the heart against acute and chronic models of cardiac stress. Cardiovascular Reserach 2019, 115, 1766-1777. doi: 10.1093/cvr/cvz076
  15. Simone Pippa, Cecilia Mannironi, Valerio Licursi, Luca Bombardi, Gianni Colotti, Enrico Cundari, Adriano Mollica, Antonio Coluccia, Valentina Naccarato, Giuseppe La Regina, Romano Silvestri, Rodolfo Negri. Small molecule inhibitors of KDM5 histone demethylases increase radio-sensitivity of breast cancer cells over-expressing JARID1B. Molecules 2019, 24, 1739-1758 (doi:10.3390/molecules24091739, IF 2017: 3098).
  16. [162] Masci, Domiziana; Hind, Charlotte; Islam, Mohammad; Toscani, Anita; Clifford, Melanie; Coluccia, Antonio; Conforti, Irene; Touitou, Meir; Memdouh, Siham; Wei, Xumin; La Regina, Giuseppe; Silvestri, Romano; Sutton, J; Castagnolo, Daniele. Switching on the activity of 1,5-diaryl-pyrrole derivatives againstdrug-resistant ESKAPE bacteria: Structure-activity relationships and mode of action studies. Eur. J. Med. Chem. 2019, 178, 500-514. Doi: 10.1016/j.ejmech.2019.05.087.
  17. [16Caroline Capdevielle, Angélique Desplat, Justine Charpentier, Francis Saggliocco, Pierre Thiebaud, Nadine Thézé, Sandrine Fédou, Katarzyna B. Hooks, Romano Silvestri, Veronique Guyonnet-Duperat, Mélina Pretel, Anne-Aurélie Raymond, Jean-William Dupuy, Christophe F. Grosset, Martin Hagedorn. HDAC inhibition induces expression of scaffolding proteins critical for tumor progression in pediatric glioma: focus on EBP50 and IRSp53. Neuro-Oncology 2019, 20, 1-13 doi: org/10.1093/neuonc/noz215.
  18. Giuseppe La Regina, Michela Puxeddu, Marianna Nalli, Daniela Vullo, Paola Gratteri, Claudiu Trandafir Supuran Alessio Nocentini, Romano Silvestri. Discovery of new 1,1’-biphenyl-4-sulfonamides as selective sub-nanomolar human carbonic anhydrase II inhibitors. ACS Med. Chem. Lett. 2019, 11, 633-637. in press. 10.1021/acsmedchemlett.9b00437.
  19. Michela Puxeddu, Hongliang Shen, Ruoli Bai, Antonio Coluccia, Marianna Nalli, Carmela Mazzoccoli, Eleonora Da Pozzo, Chiara Cavallini, Claudia Martini, Viviana Orlando, Stefano Biagioni, Cristina Mazzoni, Addolorata Maria Luce Coluccia, Ernest Hamel, Te Liu, Romano Silvestri, Giuseppe La Regina. Structure-activity relationship studies and in vitro and in vivo anticancer activity of novel 3‑aroyl-1,4-diarylpyrroles against solid tumors and hematological malignancies. Eur. J. Med. Chem 2020, 185, 111828 Article 111828. /doi.org/10.1016/j.ejmech.2019.111828.
  20. Sharon Spizzichino, Giulio Mattedi, Kate Lauder, Coralie Valle, Wahiba Aouadi, Bruno Canard, Etienne Decroly, Suzanne J.F. Kaptein, Johan Neyts, Carl Graham, Zakary Sule, David J. Barlow, Romano Silvestri, Daniele Castagnolo. Design, synthesis and discovery of novel N,N’-carbazoyl-aryl-urea inhibitors of Zika NS5 methyltransferase and virus replication. ChemMedChem 2020, 15, 1-7. doi: 10.1002/cmdc.201900533.
  21. Antonio Coluccia, Michela Puxeddu, Marianna Nalli, Chih-Ku Wei, Yu-Hsuan Wu, Eloise Mastrangelo, Tasneem Mohmmed, Delia Tarantino, Joachim Jakob Bugert, Benno Schreiner, Juliane Nolte, Frank Schwarze, Giuseppe La Regina, Jin-Ching Lee, Romano Silvestri. Discovery of new Zika Virus NS2B/NS3 inhibitors that prevent mice from life-threatening infection and brain damage. ACS Med. Chem. Lett. 2020, Publication Date: January 15, 2020. doi: org/10.1021/acsmedchemlett.9b00405. Special issue in memory of Maurizio Botta.
  22. Romina Scala, Adele Di Matteo, Antonio Coluccia, Alessandra Lo Sciuto, Luca Federici, Carlo Travaglini-Allocatelli, Paolo Visca, Romano Silvestri, Francesco Imperi. Mutational analysis of the essential lipopolysaccharide-transport protein LptH of Pseudomonas aeruginosa to uncover critical oligomerization sites. Sci. Reports 2020, accepted.
  23. Marianna Bufano, Marion Laudette, Jean-Paul Blondeau, Frank Lezoualc’h, Marianna Nalli, Romano Silvestri, Andrea Brancale, Antonio Coluccia. Modeling Epac1 Interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics. J. Comp.-Aid. Mol. Des. 2020, accepted

Invited lectures (since 2010)

• Development of new tubulin targeting agents. XX National Meeting on Medicinal Chemistry. Abano Terme, Italy, 12-16-Sep-2010 • Drug design and synthesis of non-nucleoside inhibitors of both HIV-1 wild type and resistant mutant strains reverse transcriptase, and Coxsackie B4 virus. Istitute Pasteur Italy - Fondazione Cenci Bolognetti, Ponzano Romano, Italy, 18-19-Nov-2011 • Development of new tubulin targeting agents. COST Meeting. Warsaw Poland,, 18-21-Sep-2013. • Tubulin Targeting Anti-Cancer Agents, Erberhard Karls Universität Tübingen, Pharmaceutical Chemistry. Tübingen, Germany, 14-Mar-2014 • New Tubulin Targeting Anti-Cancer Agents, Polo Oncologico "Giovanni Paolo II", Lecce, Italy, 22-Oct-2015 • Twenty years of sulfone non-nucleoside HIV-1 reverse transcriptase inhibitors, VI EWDSy, Siena, Italy, 16-19-May-2016 • Discovery of sulfone non-nucleoside HIV-1 reverse transcriptase inhibitors, King's College, London. 10-Aug-2016 • New anti-Cancer Agents through an Interaction with Tubulin. EUFEPS Annual Meeting. Athens, Greece, 26-May-2018 • New Agents Targeting ZIKA Protease or Methyl-Transferases, 16th Medical Biodefense Conference. Munich, Germany, 28-31-Oct-2018 • New anticancer agents through and interaction with tubulin, COST Meeting”Strtagem” (CA17104), Torino, Italy, 29-31-Jan-2019  

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma