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Design, Synthesis and Biological Evaluation of New 5‐(2‐Nitrophenyl)‐1‐aryl‐1 H ‐pyrazoles as Topoisomerase Inhibitors
Author(s) -
Kaur Manpreet,
Mehta Vikrant,
Arora Sahil,
Munshi Anjana,
Singh Sandeep,
Kumar Raj
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202101459
Subject(s) - cytotoxicity , topoisomerase , downregulation and upregulation , viability assay , chemistry , apoptosis , reactive oxygen species , cell cycle , cancer cell , pten , mcf 7 , cancer research , pharmacology , cancer , biochemistry , biology , enzyme , pi3k/akt/mtor pathway , in vitro , human breast , genetics , gene
5‐(2‐Nitrophenyl)‐1‐aryl‐1 H ‐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.