title: Nitrogen-containing apigenin analogs: preparation and biological activity.
abstract: A series of nitrogen-containing apigenin analogs 4a-j was synthesized via Mannich reactions to develop anticancer, antibacterial, and antioxidant agents from plant-derived flavonoids. The chemical structures of these compounds were confirmed using (1)H-NMR, (13)C-NMR, and ESI-MS. The in vitro biological 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. Compound 4i showed the most favorable in vitro antiproliferative activity with IC50 values 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 that 4i had the most potent antioxidant activity, with the smallest IC(50) value (334.8 μg/mL). The antibacterial activities of the analogs were determined using a two-fold serial dilution technique against four pathogenic bacteria, namely Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. All the prepared apigenin analogs exhibited more potent activities than the parent apigenin. Compounds 4h and 4j, in particular, exhibited the best inhibitory activities against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values of 3.91 and 1.95 μg/mL, respectively.
authors.affiliation: Colleges of Science and Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Dong-En
authors.initials: DE
authors.lastname: Wang
authors.forename: Tianyu
authors.initials: T
authors.lastname: Yao
authors.forename: Long
authors.initials: L
authors.lastname: Pang
authors.forename: Qin
authors.initials: Q
authors.lastname: Tu
authors.forename: Saeed Mahmoud
authors.initials: SM
authors.lastname: Ahmed
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Jinyi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D047310:Apigenin / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging; D008826:Microbial Sensitivity Tests; D009584:Nitrogen / Q000737:chemistry*; D010851:Picrates / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D010851:Picrates; D047310:Apigenin; C004931:1,1-diphenyl-2-picrylhydrazyl; D009584:Nitrogen