Synthesis and Biological Evaluation of Apigenin Derivatives as Antibacterial and Antiproliferative Agents

Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one] derivatives,3a–3jand4a–4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2or C3spacers, respectively. The chemical structures of the apigenin derivatives were confirmed using1H-NMR,13C-NMR, and electrospray ionization mass spectroscopy. Thein vitroantibacterial and antiproliferative activities of all synthesized compounds were determined. Among the tested compounds,4a–4jdisplayed significant antibacterial activity against the tested strains (Staphylococcus aureus,Bacillus subtilis,Escherichia coli, andPseudomonas aeruginosa). Additionally,4ishowed the best inhibitory activity with minimum inhibitory concentrations of 1.95, 3.91, 3.91, and 3.91 μg/mL againstS. aureus,B. subtilis,E. coli, andP. aeruginosa, respectively. The antiproliferative activity of the apigenin derivatives was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. We determined that4a–4jdisplayed better growth inhibition activity against four human cancer cell lines, namely, human lung (A549), human cervical (HeLa), human hepatocellular liver (HepG2), and human breast (MCF-7) cancer cells, than the parent apigenin. Compound4jwas found to be the most active antiproliferative compound against the selected cancer cells. Structure-activity relationships were also discussed based on the obtained experimental data.Keywords:synthesis;biological evaluation;apigenin derivatives;antibacterial activity;antiproliferative activity;MTT assay