Novel Furan and Furo[2,3–d]pyrimidinone Analogues: Cytotoxicity, Antioxidant, and Bleomycin‐Dependent DNA Damage Assessment

Abstract

AbstractEthyl 2‐amino‐4,5‐diphenylfuran‐3‐carboxylate (2), a reactive synthon, was successfully used to synthesize a novel series of furan and furo[2,3–d]pyrimidinone analogues by interactions with the proper chemical reagents. With the aid of precise spectroscopic data (FT‐IR, Mass, 1H‐NMR, and 13C‐NMR spectra), the structures of products were clearly established. The cytotoxic results by MTT assay showed that furo[2,3–d]pyrimidinone analogues 4 (IC50=6.1±0.8 & 10.2±2.5 μM), 6 (IC50=9.2±2.1 & 17.8±0.5 μM), 11 (IC50=7.1±0.5 & 9.2±1.8 μM), 12 (IC50=5.4±2.3 & 9.8±1.7 μM), 15 (IC50=5.2±2.0 & 8.8±2.0 μM), 18 (IC50=4.2±2.4 & 10.7±1.8 μM), and 21 (IC50=12.8±1.9 & 18.8±0.9 μM) had strong in vitro cytotoxic activities to inhibit the growth of colorectal carcinoma (HCT‐116), and prostate cancer (PC3) cell lines, respectively. However, their effects on normal lung fibroblast (WI‐38) were weak in comparison to 5‐fluorouracil as a positive control. On the other hand, the biological evaluations supported the presence of strong antioxidant activity for the furo[2,3–d]pyrimidinone analogues 4, 6, 15, 17, and 21 (% inhibition=89.10, 84.16, 82.09, 88.11, and 80.23 %, respectively) when compared to ascorbic acid (88.42 %). It has been proven that the most powerful cytotoxic and antioxidant compounds have a superior protective influence on DNA against bleomycin‐induced damage.