Earticle

초록

영어

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 μM to 150.10 μM (A549), and 13.25 μM to 50.15 μM (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.

목차

ABSTRACT
Introduction
Materials and Methods
1. Synthesis
2. Cell Culture
3. Clonogenic assay
4. DNMT1 inhibition assay
5. Statistical analysis
Results and Discussion
1. Synthesis
2. Inhibition of cell survival
3. Screening of the compounds as radiosensitizers
4. Inhibition of DNMT1 activity
Discussion
Conclusion
Acknowledgements
References

키워드

저자

• Chan Woo Wee [ Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea ]
• Jin Ho Kim [ Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea ]
• Hak Jae Kim [ Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea ]
• Hyun-Cheol Kang [ Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea ]
• Soo Youn Su [ Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea ]
• Beom Soo Shin [ School of Pharmacy, Sungkyunkwan University, Suwon, Korea ]
• Eunsook Ma [ College of Pharmacy, Daegu Catholic University, Gyeongsan, Korea ] Corresponding Author
• Il Han Kim [ Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea ] Corresponding Author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  방사선방어학회지 [Journal of Radiation Protection and Research]

• 간기

  계간

• pISSN

  2508-1888

• 수록기간

  1976~2026

• 등재여부

  KCI 등재,SCOPUS

• 십진분류

  KDC 559 DDC 629