title: Synthesis and antitumor activity of novel enediyne-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids.
abstract: A series of novel pyrrolo[2,1-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.
authors.affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Jium-Jia
authors.initials: JJ
authors.lastname: Liang
authors.forename: Chai-Lin
authors.initials: CL
authors.lastname: Kao
authors.forename: You-Chiang
authors.initials: YC
authors.lastname: Chen
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Tsai
authors.forename: Ming-Jung
authors.initials: MJ
authors.lastname: Wu
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Jeh-Jeng
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D053281:Enediynes / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C474072:(11aS)-8-hydroxy-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one; D000970:Antineoplastic Agents; D053281:Enediynes; D007211:Indoles; D009943:Organophosphorus Compounds; D016159:Tumor Suppressor Protein p53; D001569:Benzodiazepines; D053148:Caspase 3