title: A novel tetramethylnaphthalene derivative selectively inhibits adult T-cell leukemia (ATL) cells in vitro.
abstract: Adult T-cell leukemia (ATL) is caused by infection with human T-cell leukemia virus type-1 (HTLV-1). The tetrahydrotetramethylnaphthalene derivative TMNAA has recently been identified as a selective inhibitor of HTLV-1-infected T-cell lines and adult T-cell leukemia (ATL) cells but not of uninfected T-cell lines and peripheral blood mononuclear cells (PBMCs). In the present study, more than 100 derivatives of TMNAA were synthesized and examined for their inhibitory effects on the proliferation of various T-cell lines and PBMCs. Among the compounds, MN417 is a more potent inhibitor of ATL cells than TMNAA. This compound is a novel phenanthridinone derivative with the tetrahydrotetramethylnaphthalene structure. Interestingly, PN-H and MN314-B, which are also phenanthridinone derivatives but do not have the tetrahydrotetramethylnaphthalene structure, could not distinguish between HTLV-1-infected and uninfected T-cell lines in terms of their anti-proliferative activity. These results suggest that the tetrahydrotetramethylnaphthalene structure is required for the selective inhibition of HTLV-1-infected cells.
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan. m-baba@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Risa
authors.initials: R
authors.lastname: Mukai
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Mika
authors.initials: M
authors.lastname: Okamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohshima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015459:Leukemia-Lymphoma, Adult T-Cell; D009636:Norbornanes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009636:Norbornanes; C576101:tetramethylnorbornadiene
keywords: ATL; HTLV-1; inhibitor; tetramethylnaphthalene derivative