Synthesis, structural characterization and biological evaluation of 4'-C-methyl- and phenyl-dioxolane pyrimidine and purine nucleosides.
Nucleoside analogues play an important role in antiviral, antibacterial and antineoplastic chemotherapy. Herein we report the synthesis, structural characterization and biological activity of some 4'-C -methyl- and -phenyl dioxolane-based nucleosides. In particular, α and β anomers of all natural nucleosides were obtained and characterized by NMR, HR-MS and X-ray crystallography. The compounds were tested for antimicrobial activity against some representative human pathogenic fungi, bacteria and viruses. Antitumor activity was evaluated in a large variety of human cancer cell-lines. Although most of the compounds showed non-significant activity, 23α weakly inhibited HIV-1 multiplication. Moreover, 22α and 32α demonstrated a residual antineoplastic activity, interestingly linked to the unnatural α configuration. These results may provide structural insights for the design of active antiviral and antitumor agents.
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Silvia
S
Franchini
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Umberto M
UM
Battisti
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Claudia
C
Sorbi
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Annalisa
A
Tait
Department of Chemical and Geological Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Andrea
A
Cornia
College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
Lak Shin
LS
Jeong
College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
Sang Kook
SK
Lee
College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
Jayoung
J
Song
Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, CA, Italy.
Roberta
R
Loddo
Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, CA, Italy.
Silvia
S
Madeddu
Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, CA, Italy.
Giuseppina
G
Sanna
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy. livio.brasili@unimore.it.
Livio
L
Brasili
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D004148:Dioxolanes; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; C010962:formal glycol
1,3-Dioxolanes; Antitumor; Antiviral; Nucleosides; Purines; Pyrimidines; Vorbrüggen reaction