Novel chalcone-derived pyrazoles as potential therapeutic agents for the treatment of non-small cell lung cancer.

Maciejewska, Natalia; Olszewski, Mateusz; Jurasz, Jakub; Serocki, Marcin; Dzierzynska, Maria; Cekala, Katarzyna; Wieczerzak, Ewa; Baginski, Maciej

Lung cancer is considered to account for approximately one-fifth of all malignant tumor-related deaths worldwide and is therefore one of the most lethal malignancies. Pyrazole scaffold possesses a wide range of biological and pharmacological activities, which play important roles in medicinal chemistry. The present study reports the synthesis and in vitro biological characterization of nine pyrazoles derived from chalcones as potential anticancer agents for non-small cell lung cancer A-549, H226, and H460 cell lines. Most of the compounds efficiently inhibited the growth of all the tested cancer cell lines at micromolar concentrations. One of the most active compounds (PCH-1) was further evaluated for its effect on cell cycle distribution, apoptosis, migration, epithelial–mesenchymal transition, and oxidative stress. Furthermore, studies on the mechanism of action revealed that PCH-1 disrupts microtubule assembly, leading to cancer cell death. Molecular modeling studies confirmed the potent interaction of PCH-1 with the vinblastine binding site on tubulin. Overall, this study provides novel opportunities to identify anticancer agents in the pyrazole series.

CHALCONE; NON-small-cell lung carcinoma; PYRAZOLES; CELL cycle; BIOSYNTHESIS; PHARMACEUTICAL chemistry

Scientific Reports, 2022, Vol 12, Issue 1, p1

2045-2322

Academic Journal

10.1038/s41598-022-07691-6