Organosilicon compounds as adult T-cell leukemia cell proliferation inhibitors.
Aggressive forms of adult T-cell leukemia (ATL) respond poorly to conventional anticancer chemotherapy, and new lead compounds are required for the development of drugs to treat this fatal disease. Recently, we developed ATL cell-selective proliferation inhibitors based on a tetrahydrotetramethylnaphthalene (TMN) skeleton 1, and here we report the design and synthesis of silicon analogs of TMN derivatives. Among them, compound 13 showed the most potent growth-inhibitory activity towards the ATL cell line S1T, though its selectivity for S1T over the non-ATL cell line MOLT-4 was only moderate. This result, as well as computational studies, suggests that sila-substitution (C/Si exchange) is useful for structure optimization of these inhibitors.
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
Masaharu
M
Nakamura
Yotaro
Y
Matsumoto
Masaaki
M
Toyama
Masanori
M
Baba
Yuichi
Y
Hashimoto
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy; D009281:Naphthalenes / Q000737:chemistry; D017646:Organosilicon Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D055672:Static Electricity
D000970:Antineoplastic Agents; D009281:Naphthalenes; D017646:Organosilicon Compounds; C031721:naphthalene