Anticancer Activity of Pyrazoline A - D on MCF7 Breast Cancer Cell Line and Molecular Docking on Proliferation Proteins

Pyrazoline is a versatile heterocyclic compound with excellent biological activity, especially as a new therapeutic agent for anticancer. This study examined the binding of N-pyrazolines A - D in MCF7 cells to PKC, TRL7, and ERB/HER-2 proteins. N-phenyl-pyrazoline derivatives A, B, C, and D were evaluated for their anticancer activity against the MCF7 breast cancer cell line and their binding affinity to proliferation-related proteins PKC, TLR7, and ERB/HER-2, using in vitro and in silico methods. Pyrazoline C and D exhibited high anticancer activity with IC50 values of 0.43 and 1.21 µg/mL, respectively, while pyrazoline A showed moderate activity (IC50 = 86.74 µg/mL) and pyrazoline B was inactive (IC50 > 1,000 µg/mL). Molecular docking studies revealed that pyrazoline D had the best binding affinity to PKC (–9.532 kcal/mol), TLR7 (–5.964 kcal/mol), and ERB/HER-2 (–8.416 kcal/mol) compared to the other pyrazolines and native ligands. Pyrazoline C also showed better binding affinity than the native ligand for TLR7-A and similar binding affinity to PKC and ERB/HER-2. The binding interactions of pyrazolines C and D involved pi-sigma, pi-pi stacked, alkyl, pi-alkyl, and specific hydrogen-bonding interactions with key amino acid residues in the target proteins. These findings suggest that pyrazolines C and D have potential as anticancer agents with anti-proliferative activities. HIGHLIGHTS Pyrazoline C and D exhibited high anticancer activity, Pyrazoline A showed moderate activity, while pyrazoline B was inactive against MCF7 cells. Pyrazoline D had the best binding affinity to PKC, TLR7, and ERB/HER-2 proteins. Binding interactions involved pi-sigma, pi-pi stacked, alkyl, pi-alkyl, and hydrogen bonds. Pyrazolines C and D are potential anticancer agents with anti-proliferative activity. GRAPHICAL ABSTRACT