Design, synthesis, In Silico analysis, anti-inflammatory, and cytotoxicity evaluation of Novel Formyl-Pyrazoline derivatives

• A new series of pyrazolines (5a–g) were synthesized and characterized using FTIR, 1 H NMR, 13 C NMR, HRMS spectroscopy. • The ortho-nitrile substituted pyrazoline (5f) exhibited the highest edema inhibition of 52.29 % among the series. • The meta-chloro substituted pyrazoline (5d) displayed significant cytotoxicity against MCF-7 breast cancer cells with an IC₅₀ value of 14.181 µM. • Molecular docking and molecular dynamics simulation reveal favorable binding and stability of pyrazolines with COX-2 (PDB: 4COX ). • In silico ADME analysis indicated favourable pharmacokinetic properties of compounds. A novel series of formyl-pyrazoline derivatives was synthesised through a well-defined pathway utilising chalcones as key intermediates. These derivatives were characterised using 1 H NMR, 13 C NMR, FTIR and mass spectrometry. The anti-inflammatory activity was evaluated using the carrageenan-induced paw edema model, revealing a spectrum of anti-inflammatory effects ranging from 30.73 % to 52.29 %. Notably, the ortho-nitrile substituted pyrazoline (5f) exhibited superior anti-inflammatory activity, with a percentage inhibition of 52.29 %, compared to other compounds in the series. Furthermore, the cytotoxic effects on the viability of MCF-7 breast cancer cells were evaluated. Here, the meta-chloro substituted pyrazoline (5d) displayed a significant IC₅₀ value of 14.181 µM. Molecular docking was employed to explore the binding interactions of the protein-ligand complex (PDB: 4COX ), and molecular dynamics simulations confirmed the stability of the complex. Additionally, the ADME properties of the derivatives were studied to predict the pharmacokinetics of the synthesised pyrazolines.