Psammaplin A-Modified Novel Radiosensitizers for Human Lung Cancer and Glioblastoma Cells

  • Wee, Chan Woo (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kim, Jin Ho (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kim, Hak Jae (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kang, Hyun-Cheol (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Suh, Soo Youn (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Shin, Beom Soo (School of Pharmacy, Sungkyunkwan University) ;
  • Ma, Eunsook (College of Pharmacy, Daegu Catholic University) ;
  • Kim, Il Han (Department of Radiation Oncology, Seoul National University College of Medicine)
  • Received : 2018.11.30
  • Accepted : 2019.02.11
  • Published : 2019.03.31


Background: Psammaplin A (PsA) is a radiosensitizer whereas its clinical application is hampered by poor bioavailability. This study aimed to synthesize novel radiosensitizers using PsA as the lead compound. Materials and Methods: Eight homodimeric disulfides were synthesized from corresponding acid and cystamine dihydrochloride in N-hydroxysuccinimide and dicyclohexylcarbodiimide coupling conditions. One monomeric thiol analog was obtained by reduction of homodimeric disulfide with dithiothreitol. Clonogenic assay was used to measure cell survival after irradiation and drug treatment in human lung cancer (A549) and glioblastoma (U373MG) cells. Results and Discussion: Using the PsA backbone, nine compounds were synthesized. Eight compounds showed variable cytotoxicity with 50% inhibitory concentrations ranging $16.14{\mu}M$ to $150.10{\mu}M$ (A549), and $13.25{\mu}M$ to $50.15{\mu}M$ (U373MG). Four and six compounds radiosensitized A549 and U373MG cells, respectively. Two compounds that radiosensitized both cell lines were tested for its inhibitory effects on DNMT1. One of them was shown to significantly inhibit DNMT1 activity. Conclusion: Novel compounds with radiosensitizing activity were synthesized. These compounds have a great potential to serve as a basis for the development of future radiosensitizers. Further investigation is warranted for their clinical application.


Supported by : National Research Foundation of Korea, Seoul National University Hospital


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