Dibenzoxanthene-β-lactam hybrids as potential antioxidant and anticancer agents: Synthesis, biological evaluation, and docking study

Abstract

In this study, we designed and synthesized a series of β-lactam compounds bearing 14-phenyl-14H-dibenzo[a,j]xanthene moiety attached to the N-1 position of the β-lactam ring through a [2 + 2] cycloaddition process. All the synthesized compounds have been characterized by elemental analysis, Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (¹H NMR and ¹³C NMR) spectral analysis. These derivatives were evaluated for their anticancer and antioxidant activities. The in vitro anticancer activity of new compounds was examined against MCF-7 (breast cancer), HepG2 (liver hepatocellular carcinoma), and TC-1 (mouse lung epithelial) cell lines by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Notably, compounds 4c, 4e and 4 g demonstrated significant anticancer activity against TC-1 cell line. Additionally, compounds 4c, 4f and 4 g exhibited promising levels of efficacy against the MCF-7 cell line. The diphenylpicrylhydrazyl (DPPH) radical scavenging assay indicated that 4 h and 4i are more potent antioxidant agents than the Vitamin C, while 4a, 4b, 4c, and 4j exhibited moderate antioxidant capabilities. Furthermore, the docking simulations are consistent with the biological assay results, indicating that the hybrids may bind to protein targets through hydrogen bonding and other nonvalent interactions.