Synthesis and antitumor activity of novel enediyne-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids |
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| Authors: | Wan-Ping Hu Jium-Jia Liang Chai-Lin Kao You-Chiang Chen Chung-Yu Chen Feng-Yuan Tsai Ming-Jung Wu Long-Sen Chang Yeh-Long Chen Jeh-Jeng Wang |
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| Institution: | 1. Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan;2. Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan;3. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan;4. Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan;5. Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan;6. National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan |
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| Abstract: | A series of novel pyrrolo2,1-c]1,4]benzodiazepine (PBD) hybrids linked with enediyne is described. These compounds were prepared by linking C-8 of DC-81 (1) with an enediyne (10–16) through carbon chain linkers to afford PBD hybrid agents 17–23 in good yields. Most of the hybrids on human cancer cell lines exhibited higher cytotoxicity, and an increase in the sub-G1 population than 1. In a previous article, we have demonstrated that DC-81-indole conjugate agents (3–6) are potent inducers of cell apoptosis in melanoma. In the present article, we investigated whether DC-81-enediyne agents possess more cytotoxicity than 6 on human 293T cells. Our data revealed that treatment of 293T cells with DC-81-enediyne resulted in a significant increase of annexin V binding, caspase-3 degradation, and p53 arrest to identify apoptotic cells than 6. These results suggest that the DC-81-enediyne agents are more efficient in inducing apoptosis than DC-81-indole in 293T cells. |
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