title: Newly synthesized bis-benzimidazole derivatives exerting anti-tumor activity through induction of apoptosis and autophagy.
abstract: In this study, a new series of bis-benzimidazole derivatives were designed and synthesized. Most of these new compounds showed significant anti-tumor activity in vitro compared to Hoechst 33258. Among them, the most potent compound 8 had the IC(50) values of 0.56μM for HL60 (Human promyelocytic leukemia cells) tumor cell line and 0.58μM for U937 (Human leukemic monocyte lymphoma cells) tumor cell line. Subsequent toxicity study on human peripheral blood mononuclear cells (PBMC) showed that compound 8 exhibited less toxicity than 5-FU. We also found that apoptosis and autophagy were simultaneously induced by compound 8 in HL60 cells, and inhibition of autophagy by 3-MA decreased compound 8-induced apoptosis, indicating that they acted in synergy to exert tumor cell death.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Na-Ying
authors.initials: NY
authors.lastname: Chu
authors.forename: Qin-He
authors.initials: QH
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Chun-Guo
authors.initials: CG
authors.lastname: Jiang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D006690:Bisbenzimidazole