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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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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.
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참고문헌 (32)
참고문헌 신청
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Lyko F / 2005 / DNA Methyltransferase inhibitors and the development of epigenetic cancer therapies / J. Natl. Cancer. Inst 97(20):1498~1506
Manoharan M / 2007 / Epigenetic targets in the diagnosis and treatment of prostate cancer / Int. Braz. J. Urol 33(1):11~18
Lin RK / 2007 / Alteration of DNA methyltransferases contributes to 5´CpG methylation and poor prognosis in lung cancer / Lung. Cancer 55(2):205~213
Esteller M / 2003 / Relevance of DNA methylation in the management of cancer / Lancet. Oncol 4(6):351~358
Lyko F / 2005 / DNA Methyltransferase inhibitors and the development of epigenetic cancer therapies / J. Natl. Cancer. Inst 97(20):1498~1506
Manoharan M / 2007 / Epigenetic targets in the diagnosis and treatment of prostate cancer / Int. Braz. J. Urol 33(1):11~18
Lin RK / 2007 / Alteration of DNA methyltransferases contributes to 5´CpG methylation and poor prognosis in lung cancer / Lung. Cancer 55(2):205~213
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