Nitrogen-Containing Apigenin Analogs: Preparation and Biological Activity

A series of nitrogen-containing apigenin analogs4a–jwas synthesized via Mannich reactions to develop anticancer, antibacterial, and antioxidant agents from plant-derived flavonoids. The chemical structures of these compounds were confirmed using1H-NMR,13C-NMR, and ESI-MS. Thein vitrobiological activities of the analogs were evaluated via assays of their antiproliferative, antibacterial, and antioxidant activities. The prepared apigenin analogs exhibited different antiproliferative activities against four human cancer cell lines, namely human cervical (HeLa), human hepatocellular liver (HepG2), human lung (A549), and human breast (MCF-7) cancer cells. Compound4ishowed the most favorablein vitroantiproliferative activity with IC50values of 40, 40, 223, and 166 μg/mL against HeLa, HepG2, A549, and MCF-7, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity assay also showed that4ihad the most potent antioxidant activity, with the smallest IC50value (334.8 μg/mL). The antibacterial activities of the analogs were determined using a two-fold serial dilution technique against four pathogenic bacteria, namelyStaphylococcus aureus,Bacillus subtilis,Escherichia coli, andPseudomonas aeruginosa. All the prepared apigenin analogs exhibited more potent activities than the parent apigenin. Compounds4hand4j, in particular, exhibited the best inhibitory activities against the Gram-positive bacteriaStaphylococcus aureusandBacillus subtiliswith MIC values of 3.91 and 1.95 μg/mL, respectively.Keywords:apigenin analogs;antiproliferative activity;antibacterial activity;antioxidant activity