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

Abstract

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 5 e 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 5 e against Topo I and Topo II.

A Minireview on the Scope of Cadogan Cyclization Reactions Leading to Diverse Azaheterocycles

“…In 2021, our group synthesized a novel series of 1,4‐dihydropyrazolo[4,3‐ b ]indoles from various 5‐(2‐nitrophenyl)‐1 H ‐pyrazole [42] precursors through intramolecular C−N bond formation using Cadogan cyclization (Scheme 18), and performed a DFT study to support the involvement of nitrene insertion in the mechanism of the reaction. We further tested all the synthesized compounds for their anticancer activity against various cancer cell lines such as A549, HCT‐116, and MDA‐MB‐231 (breast cancer), and MCF‐7 [43] .…”