Synthesis, In Vitro Cytotoxicity and Bleomycin‐Dependent DNA Damage Evaluation of Some Heterocyclic‐Fused Pyrimidinone Derivatives

Abstract

AbstractIn this work, enaminones 1 a,b were used as precursors for the synthesis of novel fused heterocyclic ring systems (e. g. pyrazolo[3,4‐d]pyrimidinones, isoxazolo[5,4‐d]pyrimidinones, pyrimido[4,5‐d]pyrimidinones and related compounds) via their reactions with some N‐nucleophiles. The cytotoxic activity of the designed products was assessed via the MTT colorimetric assay against human liver hepatocellular carcinoma (HepG2) and normal lung fibroblasts (WI‐38) cell lines using doxorubicin as a reference standard. Among the screened compounds, pyrazolo[3,4‐d]pyrimidinone 3 d and pyrimido[4,5‐d]pyrimidinones 6 a,b, 7 b and 8 a,b were selected as lead molecules because they showed significant activity against HepG2 cells and a weak cytotoxic effect against WI‐38 cells. In further, all of the compounds were subjected to the bleomycin‐dependent DNA damage studies. The results indicated that most of them have a remarkable ability to protect DNA compared to ascorbic acid as a standard compound.