Identification by Inverse Virtual Screening of magnolol-based scaffold as new tankyrase-2 inhibitors

  • Bioorg Med Chem. 2018 Aug 7;26(14):3953-3957. doi: 10.1016/j.bmc.2018.06.019.
Simone Di Micco  1 ,  Luana Pulvirenti  2 ,  Ines Bruno  1 ,  Stefania Terracciano  1 ,  Alessandra Russo  1 ,  Maria C Vaccaro  1 ,  Dafne Ruggiero  3 ,  Vera Muccilli  2 ,  Nunzio Cardullo  2 ,  Corrado Tringali  2 ,  Raffaele Riccio  1 ,  Giuseppe Bifulco  4
Affiliations
  • 1. Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.
  • 2. Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
  • 3. Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy; PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy.
  • 4. Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy. Electronic address: [email protected].
PMID: 29934219 DOI: 10.1016/j.bmc.2018.06.019
Abstract

The natural product magnolol (1) and a selection of its bioinspired derivatives 2-5, were investigated by Inverse Virtual Screening in order to identify putative biological targets from a panel of 308 proteins involved in Cancer processes. By this in silico analysis we selected tankyrase-2 (TNKS2), Casein Kinase 2 (CK2) and bromodomain 9 (Brd9) as potential targets for experimental evaluations. The Surface Plasmon Resonance assay revealed that 3-5 present a good affinity for tankyrase-2, and, in particular, 3 showed an antiproliferative activity on A549 cells higher than the well-known tankyrase-2 inhibitor XAV939 used as reference compound.

Keywords
Anti-cancer drugs; Biomimetic compounds; Inverse Virtual Screening; Tankyrase-2; Tankyrase-2 inhibitors.