Integrated computational and preclinical evaluation of novel synthetic pyrazole pyrazoline thiazole derivative for breast cancer therapeutics

Breast cancer is the uncontrolled growth of breast cells in the lobules or the inner lining of milk ducts due to dysfunction of regulatory genes. The drugs currently used in breast cancer treatment have severe limitations. The study aimed to test 10 new synthetic forms of pyrazole clubbed pyrazoline thiazole derivatives for their ability to kill tumor cells, reduce inflammation, fight free radicals, and other important factors linked to breast cancer. The study involved computational models to assess ligand-binding affinities and pharmacokinetic properties. Later, we evaluated cytotoxicity using a human breast cancer cell line, MCF-7. In a preclinical model, the levels of vital cytokines like Transforming Growth Factor-β (TGF-β), Tumor Necrosis Factor alpha (TNF-α), and Interleukin- 6 were used to test the anticancer activity. The antioxidant activity is evaluated by malondialdehyde (MDA) levels. Changes in body weight, tumor weight and volume, inflammatory cytokine concentrations, and histology were among the measurements taken in rats. In result, we found compound 5E [5-(2-fluorophenoxy)-4-(3-(4-fluorophenyl)-1-(4-(4-fluorophenyl)thiazol-2-yl)-4,5-dihydro-1 H-pyrazol-5-yl)-3-methyl-1-phenyl-1 H-pyrazole] has best antitumor activity by decreasing the levels of TNF-α, IL-6, MDA, and TGF-β. It was observed that compound 5E contains potential in vitro and in vivo anticancer activity.