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      https://www.ias.ac.in/article/fulltext/jcsc/132/0136

    • Keywords

       

      Prostate cancer; tetrahydrofuran cyclic urea; androgen receptor antagonist; oxetane; hydantoin

    • Abstract

       

      In order to improve the antiproliferative activity of androgen receptor (AR) antagonists, which used clinically for the treatment of prostate cancer that is a major cause of male death in worldwide, we report the design and synthesis of a series of tetrahydrofuran cyclic urea-based non-steroidal small molecule ARantagonists and exhibit potent AR antagonistic activity. These molecules with higher stereochemical aspects have been achieved by changing the hydantoin analogue antiandrogens to 4-(2-oxohexahydro-1H-furo[3,4-d] imidazol-1-yl)-2-(trifluoromethyl)benzonitrile analogues. Here, the thio-hydantoin pharmacophore of the recently reported antagonists is replaced by tetrahydrofuran cyclic urea. The antiproliferative properties ofthese molecules have been evaluated against androgen-dependent (LNCaP) cell line. Among the reported molecules, 4-(2-oxohexahydro-1H-furo[3,4-d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile (AR04) showed significantly improved in vitro activity, IC50 = 3.926 lM. Molecular structure-activity relationship studiesconfirm that the oxetane analogue AR04 is distinct from other synthesized AR antagonists. These results have suggested that AR04 exhibiting their potential as a lead compound for the alternative treatment of prostate cancer.

    • Author Affiliations

       

      MURALIKRISHNA YARAGANI1 PRASAD YADLAPALLI2 SRIRAM RAGHAVAN3 NIRAIKULAM AYYADURAI4 SARAVANAN CHINNUSAMY5 VENKATA BASAVESWARA RAO MANDAVA6 RAJASEKHARA PRASAD KOTTAPALLI1

      1. Department of Chemistry, Koneru Lakshmaiah Education Foundation, Guntur, Andhra Pradesh 522 502, India
      2. GVK Biosciences Pvt. Ltd, Hyderabad, Telangana 500 076, India
      3. CAS in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, Tamil Nadu 600 020, India
      4. Department of Biochemistry and Biotechnology, CSIR-Central Leather Research Institute, Adyar, Chennai 600 020, Tamil Nadu, India
      5. Department of Chemistry, Center for Advanced Organic Materials (Sona-AROMA), Sona College of Technology, Salem, Tamil Nadu 636 005, India
      6. Department of Chemistry, Krishna University, Krishna, Andhra Pradesh 521 001, India
    • Dates

       
  • Journal of Chemical Sciences | News

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