具有1,2,3-三唑连接基的膦酰化无环鸟苷类似物

Głowacka Iwona E, Andrei Graciela, Schols Dominique, Snoeck Robert, Piotrowska Dorota G

Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Muszyńskiego 1, Poland.

Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.

Molecules. 2015 Oct 16;20(10):18789-807. doi: 10.3390/molecules201018789.

A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80-210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50=15-30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.

合成了一系列新型的{4-[(2-氨基-6-氯-9H-嘌呤-9-基)甲基]-1H-1,2,3-三唑-1-基}烷基膦酸酯和{4-[(2-氨基-6-氧代-1,6-二氢-9H-嘌呤-9-基)甲基]-1H-1,2,3-三唑-1-基}烷基膦酸酯，作为鸟苷的无环类似物，并评估了它们对多种DNA和RNA病毒的抗病毒活性以及对三种癌细胞系（HeLa、L1210和CEM）的细胞生长抑制活性。它们没有抗病毒活性；然而，发现几种膦酸酯在80-210 μM范围内对HeLa细胞有轻微的细胞生长抑制作用。化合物(1R,2S)-17k和(1S,2S)-17k对小鼠白血病（L1210）和人T淋巴细胞（CEM）细胞系的增殖表现出最高的抑制作用（IC50=15-30 μM）。