Franchini Silvia, Battisti Umberto M, Sorbi Claudia, Tait Annalisa, Cornia Andrea, Jeong Lak Shin, Lee Sang Kook, Song Jayoung, Loddo Roberta, Madeddu Silvia, Sanna Giuseppina, Brasili Livio
Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Department of Chemical and Geological Sciences, University of Modena & Reggio Emilia, Via G. Campi 103, 41125, Modena, Italy.
Arch Pharm Res. 2017 May;40(5):537-549. doi: 10.1007/s12272-016-0825-6. Epub 2016 Sep 11.
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.
核苷类似物在抗病毒、抗菌和抗肿瘤化疗中发挥着重要作用。在此，我们报道了一些基于4'-C-甲基和苯基二氧戊环的核苷的合成、结构表征及生物活性。特别地，获得了所有天然核苷的α和β异头物，并通过核磁共振（NMR）、高分辨质谱（HR-MS）和X射线晶体学对其进行了表征。测试了这些化合物对一些代表性人类致病真菌、细菌和病毒的抗菌活性。在多种人类癌细胞系中评估了其抗肿瘤活性。尽管大多数化合物显示出无显著活性，但23α对HIV-1增殖有微弱抑制作用。此外，22α和32α表现出残余的抗肿瘤活性，有趣的是，这与非天然的α构型有关。这些结果可为设计活性抗病毒和抗肿瘤药物提供结构方面的见解。
