ComputOrgChem Unisa

Drug Design

Introduction

Computer-Aided Drug Design (CADD) methods are applied in our research, namely structure-based drug design (SBDD) and ligand-based drug design (LBDD) to identify new promising anticancer and anti-inflammatory compounds. We use methodologies like pharmacophore modeling, similarity search, and fragment build to collect the information necessary for the design of new combinatorial libraries and their evaluation after molecular docking calculations. Specifically, our research is focused on the pharmacological target BRD9, mPGES-1, and sEH, involved in inflammation and cancer.

Latest papers:

  • Lauro, G.; Terracciano, S.; Cantone, V.; Ruggiero, D.; Fischer, K.; Pace, S.; Werz, O.; Bruno, I.; Bifulco, G., A Combinatorial Virtual Screening Approach Driving the Synthesis of 2,4-Thiazolidinedione-Based Molecules as New Dual mPGES-1/5-LO Inhibitors. ChemMedChem 2020, 15, 481-489. https://doi.org/10.1002/cmdc.201900694
  • Chini, M. G.; Giordano, A.; Potenza, M.; Terracciano, S.; Fischer, K.; Vaccaro, M. C.; Colarusso, E.; Bruno, I.; Riccio, R.; Koeberle, A.; Werz, O.; Bifulco, G., Targeting mPGES-1 by a Combinatorial Approach: Identification of the Aminobenzothiazole Scaffold to Suppress PGE2Levels. ACS Med. Chem. Lett. 2020, 11, 783-789. https://doi.org/10.1021/acsmedchemlett.9b00618
  • Bertamino, A.; Ostacolo, C.; Medina, A.; Di Sarno, V.; Lauro, G.; Ciaglia, T.; Vestuto, V.; Pepe, G.; Basilicata, M. G.; Musella, S.; Smaldone, G.; Cristiano, C.; Gonzalez-Rodriguez, S.; Fernandez-Carvajal, A.; Bifulco, G.; Campiglia, P.; Gomez-Monterrey, I.; Russo, R., Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their in Vitro Characterization and in Vivo Analgesic Activities. J. Med. Chem. 2020, 63, 9672-9694. https://doi.org/10.1021/acs.jmedchem.0c00816
  • Nemati, F.; Salehi, P.; Bararjanian, M.; Hadian, N.; Mohebbi, M.; Lauro, G.; Ruggiero, D.; Terracciano, S.; Bifulco, G.; Bruno, I., Discovery of noscapine derivatives as potential β-tubulin inhibitors. Bioorg. Med. Chem. Lett. 2020, 30, 127489. https://doi.org/10.1016/j.bmcl.2020.127489
  • D’Ambola, M.; Fiengo, L.; Chini, M. G.; Cotugno, R.; Bader, A.; Bifulco, G.; Braca, A.; De Tommasi, N.; Dal Piaz, F., Fusicoccane Diterpenes from Hypoestes forsskaolii as Heat Shock Protein 90 (Hsp90) Modulators. J. Nat. Prod. 2019, 82, 539-549. https://doi.org/10.1021/acs.jnatprod.8b00924
  • Ostacolo, C.; Di Sarno, V.; Lauro, G.; Pepe, G.; Musella, S.; Ciaglia, T.; Vestuto, V.; Autore, G.; Bifulco, G.; Marzocco, S.; Campiglia, P.; Gomez-Monterrey, I. M.; Bertamino, A., Identification of an indol-based multi-target kinase inhibitor through phenotype screening and target fishing using inverse virtual screening approach. Eur. J. Med. Chem. 2019, 167, 61-75. https://doi.org/10.1016/j.ejmech.2019.01.066
  • Gerstmeier, J.; Kretzer, C.; Di Micco, S.; Miek, L.; Butschek, H.; Cantone, V.; Bilancia, R.; Rizza, R.; Troisi, F.; Cardullo, N.; Tringali, C.; Ialenti, A.; Rossi, A.; Bifulco, G.; Werz, O.; Pace, S., Novel benzoxanthene lignans that favorably modulate lipid mediator biosynthesis: A promising pharmacological strategy for anti-inflammatory therapy. Biochem. Pharmacol. 2019, 165, 263-274. https://doi.org/10.1016/j.bcp.2019.03.003
  • Di Micco, S.; Masullo, M.; Bandak, A. F.; Berger, J. M.; Riccio, R.; Piacente, S.; Bifulco, G., Garcinol and Related Polyisoprenylated Benzophenones as Topoisomerase II Inhibitors: Biochemical and Molecular Modeling Studies. J. Nat. Prod. 2019, 82, 2768-2779. https://doi.org/10.1021/acs.jnatprod.9b00382
  • Lauro, G.; Cantone, V.; Potenza, M.; Fischer, K.; Koeberle, A.; Werz, O.; Riccio, R.; Bifulco, G., Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol. MedChemComm 2018, 9, 2028-2036. https://doi.org/10.1039/c8md00497h
  • Di Micco, S.; Terracciano, S.; Cantone, V.; Fischer, K.; Koeberle, A.; Foglia, A.; Riccio, R.; Werz, O.; Bruno, I.; Bifulco, G., Discovery of new potent molecular entities able to inhibit mPGES-1. Eur. J. Med. Chem. 2018, 143, 1419-1427. https://doi.org/10.1016/j.ejmech.2017.10.039