title: Thiophene-expanded guanosine analogues of Gemcitabine.
abstract: The chemotherapeutic drug Gemcitabine, 2',2'-difluoro-2'-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic properties stem from its 2',2'-difluoro-2'-deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition).
authors: University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
authors: Zhe
authors: Z
authors: Chen
authors: University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
authors: Therese C
authors: TC
authors: Ku
authors: University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: kseley@umbc.edu.
authors: Katherine L
authors: KL
authors: Seley-Radtke
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D013876:Thiophenes; D003841:Deoxycytidine; D006151:Guanosine; D000093542:Gemcitabine
keywords: 2′,2′-Difluoro-2′-deoxycytidine; Cancer; Expanded guanosine; Nucleosides; Tricyclic