title: Synthesis of diethylamino-curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells.
abstract: A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors.
authors: Department of Hematology and oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 210-711, Republic of Korea.
authors: Yongchel
authors: Y
authors: Ahn
authors: Department of Basic Science, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea.
authors: Sangtae
authors: S
authors: Oh
authors: Department of Basic Science, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea.
authors: Seong Jun
authors: SJ
authors: Lee
authors: Department of physiology, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea.
authors: Byong-Gon
authors: BG
authors: Park
authors: Department of Microbiology, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea.
authors: Yoon-Sun
authors: YS
authors: Park
authors: Department of Microbiology, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea.
authors: Woon-Seob
authors: WS
authors: Shin
authors: Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 210-711, Republic of Korea.
authors: Hyuk Jai
authors: HJ
authors: Jang
authors: Department of Neurosurgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 210-711, Republic of Korea.
authors: Jin Hoon
authors: JH
authors: Park
authors: Department of Microbiology, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea. Electronic address: dkwon@kd.ac.kr.
authors: Daeho
authors: D
authors: Kwon
authors: Department of Pharmacology, Kwandong University College of Medicine, Gangneung 210-701, Republic of Korea. Electronic address: sjlee@kd.ac.kr.
authors: Seokjoon
authors: S
authors: Lee
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry*; D004048:Diethylamines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D004048:Diethylamines; D053221:TNF-Related Apoptosis-Inducing Ligand; D014230:Triazoles; D003474:Curcumin
keywords: Anticancer; Brain tumor; Curcumin; Curcumin mimics; TRAIL