title: Design, Synthesis and Biological Evaluation of Novel 1, 3- thiazolidine-2, 4-diones as Anti-prostate Cancer Agents.
abstract: Androgen receptor is an attractive target for the treatment of prostate cancer. The 1,3- thiazolidine-2,4-diones possess a wide diversity of important biochemical effects and interesting pharmacological properties.
  
  
  
  The aim of the study is to find the experimental and computational methods to investigate the interference of 1,3-thiazolidine-2,4-diones with androgen receptor against prostate cancer.
  
  
  
  Structural modification and molecular docking-based virtual screening approaches were imposed to identify the novel 1,3-thiazolidine-2,4-diones by using Schrödinger (Maestro 9.5). The best fit molecules (3-12 & 23-31) were synthesized and characterized using spectroscopic techniques, then in vitro antioxidant and antiprostate cancer activities were evaluated. Further, the structure of the intermediate (18) was confirmed by single crystal XRD analysis. The mechanism studies were performed through the gene expression for the compounds, 29, 30, and 31, the standards, dihydrotestosterone and R-bicalutamide.
  
  
  
  The compounds, 29, 30 and 31 showed comparatively significant antioxidant activity and better antiproliferative activity against PC-3 and LNCaP cell lines. Also, very low cytotoxicity was observed in the noncancerous cell (3T3). The compounds, 29, 30 and 31 significantly decreased the mRNA expression of ARstimulated genes, PSA and TMPRSS2, which demonstrated their anti-prostate cancer activities. ADME/T properties prediction of the compounds (3-12 and23-31) showed the promising drug-likeness and pharmacokinetic parameters without toxicity. Moreover, DFT calculations apparently confirmed the stable conformer of the compound, 31.
  
  
  
  These findings may provide the essential information for the development of anti-prostate cancer agents.
authors.affiliation: Division of Life Sciences, Institute of Advanced Study in Science and Technology, Guwahati-781035, Assam. India.
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Elancheran
authors.affiliation: Department of Chemistry, Annamalai University, Annamalai Nagar-608002, Tamil Nadu. India.
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Saravanan
authors.affiliation: Department of Pharmacology, PSG College of Pharmacy, Coimbatore-641 004, Tamil Nadu. India.
authors.forename: Selvaraj
authors.initials: S
authors.lastname: Divakar
authors.affiliation: Division of Life Sciences, Institute of Advanced Study in Science and Technology, Guwahati-781035, Assam. India.
authors.forename: Sima
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Division of Life Sciences, Institute of Advanced Study in Science and Technology, Guwahati-781035, Assam. India.
authors.forename: V Lenin
authors.initials: VL
authors.lastname: Maruthanila
authors.affiliation: Department of Chemistry, Annamalai University, Annamalai Nagar-608002, Tamil Nadu. India.
authors.forename: Senthamarikannan
authors.initials: S
authors.lastname: Kabilan
authors.affiliation: Department of Pharmacology, PSG College of Pharmacy, Coimbatore-641 004, Tamil Nadu. India.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Ramanathan
authors.affiliation: Division of Life Sciences, Institute of Advanced Study in Science and Technology, Guwahati-781035, Assam. India.
authors.forename: Rajlakshmi
authors.initials: R
authors.lastname: Devi
authors.affiliation: Division of Life Sciences, Institute of Advanced Study in Science and Technology, Guwahati-781035, Assam. India.
authors.forename: Jibon
authors.initials: J
authors.lastname: Kotoky
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D011471:Prostatic Neoplasms / Q000473:pathology*; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053778:Thiazolidines
keywords: ADME/T; AR antagonist; Androgen receptor; prostate cancer; synthesis; thiazolidinedione