ADMET properties, bioactivity and molecular docking studies of newly synthesized 5-(substituted phenyl)-3-(2(substituted) ethenyl-4,5-dihydro-1 H-pyrazole-1-carbaldehyde derivatives

A series of pyrazoline analogues (4a-4h) prepared from respective dibenzylideneacetones, (3a-3h) was studied as potential anticancer agents. Dibenzylideneacetone analogues were synthesized from acetone and excess moles of aromatic/heteroaromatic aldehydes, which were further cyclized into pyrazolines with the help of hydrazine in the presence of formaldehyde. In-vitro anti-cancer activity was performed against thehuman breast cancer cell line (MCF7) by using MTT assay. The compound 4b [5-(4-fluorophenyl)-3-[(E)-2-(4-fluorophenyl) ethenyl]-4,5-dihydro-1H-pyrazole-1- carbaldehyde] and compound 4d [5-(4-methylphenyl)-3-[(E)-2-(4-methylphenyl) ethenyl]-4,5-dihydro-1H-pyrazole-1- carbaldehyde] were found to be the moderately active with IC₅₀ of 38.49±0.17μM and 35.49±2.44 μM respectively. The molecular docking studies were conducted forthe newly synthesized molecules with the AutoDock 4.2.6 docking program. All eight derivatives were determined by the EGFR receptor (PDB ID 1M17) active binding domain, with binding energies ranging from -7.4 to -9.27 Kcal/mol.