Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates

A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC(50) (50% effective concentration) = 27.6–91.5 μM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK(−)) VZV strain (EC(50) = 27.59 μM), while 16d was the most potent towards TK(+) VZV (EC(50) = 29.91 μM). Cytostatic properties of the compounds 14a–i–17a–i were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC(50) (50% inhibitory concentration) = 29–130 µM] and L1210 cells [IC(50) (50% inhibitory concentration) = 14–142 µM].