2. Academic Validation
  3. Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide

Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide

  • Bioorg Med Chem Lett. 2014 Nov 1;24(21):4948-53. doi: 10.1016/j.bmcl.2014.09.036.
Jarrad M Altimari 1,  Birunthi Niranjan 2,  Gail P Risbridger 2,  Stephanie S Schweiker 3,  Anna E Lohning 3,  Luke C Henderson 4
Affiliations

Affiliations

  • 1 Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds Campus, Geelong 3216, Victoria, Australia; Institute for Frontier Materials, Deakin University, Pigdons Road, Waurn Ponds Campus, Geelong 3216, Victoria, Australia.
  • 2 Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria 3800, Australia.
  • 3 Faculty of Health Sciences and Medicine, Bond University, Gold Coast 4229, Queensland, Australia.
  • 4 Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds Campus, Geelong 3216, Victoria, Australia; Institute for Frontier Materials, Deakin University, Pigdons Road, Waurn Ponds Campus, Geelong 3216, Victoria, Australia. Electronic address: [email protected].
PMID: 25301770 DOI: 10.1016/j.bmcl.2014.09.036
Abstract

A versatile and high yielding synthesis of novel Androgen Receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferative properties against androgen dependent (LNCaP) and independent (PC-3) cells showed promising IC50 values of 34-45 μM and 29-151 μM, respectively. The data suggest that the latter compounds may be an excellent starting point for the development of prostate Cancer therapeutics for both androgen dependent and independent forms of this disease. Docking of these compounds (each enantiomer) in silico into the T877A mutated Androgen Receptor, as possessed by LNCaP cells, was also undertaken.

Keywords

Androgen receptor; Bicalutamide; Click chemistry; Molecular modeling; Prostate cancer; Triazole.

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