title: Squarate-based carbocyclic nucleosides: Syntheses, computational analyses and anticancer/antiviral evaluation.
abstract: Squaric acid and its derivatives are versatile synthons and have demonstrated applications in medicinal chemistry, notably as non-classical bioisosteric replacements for functional groups such as carboxylic acids, alpha-amino acids, urea, guanidine, peptide bonds and phosphate/pyrophosphate linkages. Surprisingly, no reports have appeared concerning its possible application as a nucleobase substitute in nucleosides. A preliminary investigation of such an application is reported herein. 3-Amino-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione, 3-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-4-methoxycyclobut-3-ene-1,2-dione, and 3-hydroxy-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione sodium salt were synthesized. Computational analyses of their structures and preliminary antitumor and antiviral screening results are reported.
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada; Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Meijun
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Qing-Bin
authors.initials: QB
authors.lastname: Lu
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address: jhonek@uwaterloo.ca.
authors.forename: John F
authors.initials: JF
authors.lastname: Honek
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003503:Cyclobutanes; D009705:Nucleosides; C030042:squaric acid
keywords: Anticancer; Antiviral; Bioisostere; Carbocyclic; Nucleoside; Squaric acid