2. Academic Validation
  3. Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives

Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives

  • Eur J Med Chem. 2020 Jan 1;185:111833. doi: 10.1016/j.ejmech.2019.111833.
Nataša Perin 1,  Valentina Rep 1,  Irena Sović 1,  Štefica Juričić 1,  Danijel Selgrad 2,  Marko Klobučar 2,  Nataša Pržulj 3,  Chhedi Lal Gupta 4,  Noël Malod-Dognin 5,  Sandra Kraljević Pavelić 6,  Marijana Hranjec 7
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev Trg 19, HR-10000, Zagreb, Croatia.
  • 2 Department of Biotechnology, Centre for High-throughput Technologies, University of Rijeka, Radmile Matejčić 2, HR-51000, Rijeka, Croatia.
  • 3 Department of Computer Science, University College London, London, UK; Barcelona Supercomputing Center (BSC), Barcelona, Spain; ICREA, Pg. Lluis Companys 23, 08010, Barcelona, Spain.
  • 4 Department of Computer Science, University College London, London, UK.
  • 5 Department of Computer Science, University College London, London, UK; Barcelona Supercomputing Center (BSC), Barcelona, Spain.
  • 6 Department of Biotechnology, Centre for High-throughput Technologies, University of Rijeka, Radmile Matejčić 2, HR-51000, Rijeka, Croatia. Electronic address: sandrakp@biotech.uniri.hr.
  • 7 Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev Trg 19, HR-10000, Zagreb, Croatia. Electronic address: mhranjec@fkit.hr.
PMID: 31734024 DOI: 10.1016/j.ejmech.2019.111833
Abstract

Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human Cancer cell lines. Tested compounds showed moderate activity against Cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 μM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11.

Keywords

Amides; Amines; Antiproliferative activity; Mode of action analysis; Naphtho[2,1-b]thiophenes; Phenatrenes.

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