Design, Synthesis and Biological Evaluation of New 5-(2- Nitrophenyl)-1-aryl-1H-pyrazoles as Topoisomerase Inhibitors

摘要

5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles are designed as topoisomerase (Topo) inhibitors, synthesised and assessed for their anticancer properties against breast (MDA-MB-231 and MCF7), lung (A549), and colorectal (HCT116) cancer cell lines. All the compounds induced significant cytotoxicity at low micromolar concentration. The compound 5e exerted potential anticancer effects on breast cancer cell lines at a low micromolar level (IC_(50) < 2 μM), and showed negligible toxicity towards normal cells. Compound 5e reduced reactive oxygen species (ROS) level in breast cancer cells, altered mitochondrial membrane potential and induced the cell cycle arrest at the G2/M phase. This was accompanied by downregulation of oncogenic p-Akt and upregulation of p-PTEN along with modulation of apoptotic markers suggesting multiple mechanisms to reduce cancer cell viability. Finally, the topoisomerase inhibition assay revealed the inhibitory activity of 5e against Topo I and Topo II.