title: Synthesis, DNA-binding abilities and anticancer activities of triazole-pyrrolo[2,1-c][1,4]benzodiazepines hybrid scaffolds.
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.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Lee
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Lin
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Yu
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Hsu
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.forename: Cheng-Tien
authors.initials: CT
authors.lastname: Hsiao
authors.forename: Jeh-Jeng
authors.initials: JJ
authors.lastname: Wang
authors.forename: Mei-Ing
authors.initials: MI
authors.lastname: Chung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D014230:Triazoles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D019938:Cyclin D1; D004247:DNA
keywords: Anticancer; Apoptosis; Cytotoxicity; Pyrrolo[2,1-c][1,4]benzodiazepine; Triazole