Design, synthesis and biological evaluation of 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives as anti-prostate cancer agents.
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.
Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India.
K
K
Saravanan
Drug Discovery Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati 781035, Assam, India.
R
R
Elancheran
Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641004, Tamil Nadu, India.
S
S
Divakar
Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India.
S Athavan Alias
SA
Anand
Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641004, Tamil Nadu, India.
M
M
Ramanathan
Drug Discovery Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati 781035, Assam, India.
Jibon
J
Kotoky
Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570 006, India.
N K
NK
Lokanath
Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India. Electronic address: profdrskabilanau@gmail.com.
S
S
Kabilan
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D007211:Indoles
AR antagonist; Androgen receptor; Isoindolinediones; Molecular docking; Prostate cancer