title: Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.
abstract: Nucleoside, nucleotide, and base analogs have been in the clinic for decades to treat both viral pathogens and neoplasms. More than 20% of patients on anticancer chemotherapy have been treated with one or more of these analogs. This review focuses on the chemical synthesis and biology of anticancer nucleoside, nucleotide, and base analogs that are FDA-approved and in clinical development since 2000. We highlight the cellular biology and clinical biology of analogs, drug resistance mechanisms, and compound specificity towards different cancer types. Furthermore, we explore analog syntheses as well as improved and scale-up syntheses. We conclude with a discussion on what might lie ahead for medicinal chemists, biologists, and physicians as they try to improve analog efficacy through prodrug strategies and drug combinations.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Jadd
authors.initials: J
authors.lastname: Shelton
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hollenbaugh
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Franck
authors.initials: F
authors.lastname: Amblard
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , 1760 Haygood Drive, NE, Atlanta, Georgia 30322, United States.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D009705:Nucleosides / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009705:Nucleosides; D009711:Nucleotides