title: New carbocyclic N(6)-substituted adenine and pyrimidine nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, antiviral, anticancer activity and X-ray crystallography.
abstract: New nucleoside analogues with an optically active bicyclo[2.2.1]heptane skeleton as sugar moiety and 6-substituted adenine were synthesized by alkylation of 6-chloropurine intermediate. Thymine and uracil analogs were synthesized by building the pyrimidine ring on amine 1. X-ray crystallography confirmed an exo-coupling of the thymine to the ring and an L configuration of the nucleoside analogue. The library of compounds was tested for their inhibitory activity against influenza virus A∖California/07/09 (H1N1)pdm09 and coxsackievirus B4 in cell culture. Compounds 13a and 13d are the most promising for their antiviral activity against influenza, and compound 3c against coxsackievirus B4. Compounds 3b and 3g were tested for anticancer activity.
authors.affiliation: National Institute for Chemical-Pharmaceutical Research and Development, 112 Vitan Av., 031299 Bucharest 3, Romania. Electronic address: cvtanase@gmail.com.
authors.forename: Constantin I
authors.initials: CI
authors.lastname: Tănase
authors.affiliation: Organic Chemistry Center 'C.D.Neniţescu, 202 B Splaiul Independentei, Bucharest 060023, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Drăghici
authors.affiliation: National Institute for Chemical-Pharmaceutical Research and Development, 112 Vitan Av., 031299 Bucharest 3, Romania.
authors.forename: Ana
authors.initials: A
authors.lastname: Cojocaru
authors.affiliation: Influenza Research Institute, Dept. Chemotherapy, 15/17 Prof. Popova Str., St. Petersburg 197376, Russian Federation. Electronic address: nastyagalochkina@yandex.ru.
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Galochkina
authors.affiliation: Influenza Research Institute, Dept. Chemotherapy, 15/17 Prof. Popova Str., St. Petersburg 197376, Russian Federation. Electronic address: deina89@mail.ru.
authors.forename: Jana R
authors.initials: JR
authors.lastname: Orshanskaya
authors.affiliation: Influenza Research Institute, Dept. Chemotherapy, 15/17 Prof. Popova Str., St. Petersburg 197376, Russian Federation. Electronic address: zarubaev@influenza.spb.ru.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zarubaev
authors.affiliation: Institute of Macromolecular Chemistry 'Petru Poni', Iasi, Romania.
authors.forename: Sergiu
authors.initials: S
authors.lastname: Shova
authors.affiliation: Central Laboratory for Phytosanitary Quarantine, 11, Voluntari Blvd., 077190 Voluntari, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Enache
authors.affiliation: Organic Chemistry Center 'C.D.Neniţescu, 202 B Splaiul Independentei, Bucharest 060023, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Maganu
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D029822:Enterovirus B, Human / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D061985:Madin Darby Canine Kidney Cells; D008968:Molecular Conformation; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; D011741:Pyrimidine Nucleosides; C116378:bicyclo(2.2.1)heptene
keywords: Anticancer; Antiviral activity; Bicyclo[2.2.1]heptane nucleosides; Chloropurine; Pyrimidine nucleosides; X-ray-crystallography