Design, synthesis and biological evaluation of 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives as anti-prostate cancer agents

• Published in: Bioorganic & medicinal chemistry letters 2017-03, Vol.27 (5), p.1199-1204
• Main Authors: Saravanan, K., Elancheran, R., Divakar, S., Anand, S. Athavan Alias, Ramanathan, M., Kotoky, Jibon, Lokanath, N.K., Kabilan, S.
• Format: Article
• Language: English
• Subjects: Androgen receptor; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; AR antagonist; Crystallography, X-Ray; Drug Design; Drug Screening Assays, Antitumor; Humans; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Isoindolinediones; Male; Molecular docking; Prostate cancer; Prostatic Neoplasms - pathology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.01.065

[Display omitted] The structural modification and molecular docking-based screening approaches on thiazole-based isoindolinediones were imposed to find the novel 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives. The best fit compounds (6a-n) were synthesized and evaluated their antiproliferative activities on the prostate cancer cell lines (PC-3 & LNCaP). Among them, the compound, 6m exhibited good activity, particularly on LNCaP (IC50=5.96±1.6μM), moderately active against PC-3 cell lines as compared to bicalutamide. The compound, 6m decreased the androgen-mediated transcription of ARE-mRNA in PSA, TMPRSS2, c-myc and cyclin D1 than R-bicalutamide. The compounds, 6e and 6f were reconfirmed through single crystal XRD analysis. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. These findings may provide vital information for the development of anti-prostate cancer agents.