title: Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy.
abstract: Hypermethylation of tumor suppressor genes caused by aberrant activity of DNA methyltransferases is an important mechanism that contributes to cancer. The reaction mechanism of DNA methyltransferases, which includes formation of a covalent intermediate between the enzyme and the target base, is the basis of the success of several anti-cancer drugs that are targeted against DNA methylation. These include 5-fluoro-2'-deoxycytidine, 5-aza-2'-deoxycytidine (Decitabine) and 2-H pyrimidinone-1-beta-D(2'-deoxyriboside) (Zebularine). This review provides an insight to how the chemistry of DNA methylation is involved in the performance of these drugs targeted against it.
authors.affiliation: School of Engineering and Science, International University Bremen, Bremen 28759, Germany.
authors.forename: Humaira
authors.initials: H
authors.lastname: Gowher
authors.forename: Albert
authors.initials: A
authors.lastname: Jeltsch
mesh_terms: D000818:Animals; D003562:Cytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019175:DNA Methylation; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*
chemical_list: D003562:Cytidine; D004248:DNA (Cytosine-5-)-Methyltransferases