title: Design, synthesis, inhibitory activity, and binding mode study of novel DNA methyltransferase 1 inhibitors.
abstract: To identify novel non-nucleoside DNA methyltransferase (DNMT) inhibitors, we designed and synthesized a series of maleimide derivatives. Among this series, compounds 5-8 were found to be more potent DNMT1 inhibitors than RG108, a DNMT1 inhibitor reported previously by Siedlecki et al. The binding mode analysis of compound 5 is also reported.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Rikako
authors.initials: R
authors.lastname: Tanaka
authors.forename: Shohei
authors.initials: S
authors.lastname: Hamada
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
mesh_terms: D018360:Crystallography, X-Ray; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D008301:Maleimides / Q000138:chemical synthesis* / Q000378:metabolism*; D010797:Phthalimides; D011422:Propionates / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D014364:Tryptophan / Q000031:analogs & derivatives
chemical_list: D007211:Indoles; D008301:Maleimides; D010797:Phthalimides; D011422:Propionates; C503639:RG108; D014364:Tryptophan; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human