Synthesis,DNA-binding abilities and anticancer activities of triazole-pyrrolo[2,1-c][1,4]benzodiazepines hybrid scaffolds |
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| Authors: | Chung-Yu Chen Pei-Hua Lee Yong-Yong Lin Wen-Ting Yu Wan-Ping Hu Chia-Chen Hsu Ying-Ting Lin Long-Sen Chang Cheng-Tien Hsiao Jeh-Jeng Wang Mei-Ing Chung |
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| Affiliation: | 1. Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung City 807, Taiwan;2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung City 807, Taiwan;3. Department of Biotechnology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung City 807, Taiwan;4. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung City, Taiwan |
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| Abstract: | We synthesized a new series of PBD-hybrid derivatives having tethered triazoles and investigated for their cytotoxicity. The studies indicated that cis-olefin compounds induce higher cytotoxicity with increase in the G1 cell cycle phase compared with the trans-compounds. Quantitative RT-PCR assay indicated that compounds (16a–d) induced G1 phase arrest through down-regulation of cyclin D1 and up-regulation of p21, p27, and p53 mRNA expressions. Compounds 16a–d induced A375 early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide. Moreover, the Western blot analysis showed that A375 treated by compounds (16a–d) resulted in decreased levels of Bcl-2 and Bcl-xL, increased levels of Bax and Bad, and caspase/PARP degradation to identify apoptotic cells. |
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| Keywords: | Triazole Apoptosis Cytotoxicity Anticancer |
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