Design, molecular modelling, synthesis, characterization studies of novel N-(7-(substituted benzylidene)-4-phenyl-4,5,6,7-tetrahydro-3H-cyclopenta[d]pyrimidin-2-yl)-1-(substituted phenyl)methanimine against breast cancer

A designed seventy-five distinct group of compounds namely N-(7-(substituted benzylidene)-4-phenyl-4,5,6,7-tetrahydro-3H-cyclopenta[d]pyrimidin-2-yl)-1-(substitutedphenyl) methanimine underwent evaluation for their potential against breast cancer utilizing various methods such as computational docking and dynamics, synthetic processes, structural characterization, and in vitro testing. The compound known as 2a3 was pinpointed through several analyses including elemental, HR-MS, FT-IR, 1H NMR, and 13C NMR. The online platform SwissADME predicted its physicochemical, drug-like, and pharmacokinetic profiles. Identification of drug targets was achieved using a network pharmacology technique, and extensive molecular docking tests were conducted to analyse how well the ligand and its complexes interacted with 23 specific breast cancer targets. These experiments revealed that the 2a3 complex demonstrated superior binding energy and interaction capabilities. Remarkably, 3LFF (Human p38 kinase), 5EW8 (Fibroblast growth factor receptor), 6E2N (MAPK), 6WW8 (CDK4/6 receptor), 7PCD (HER2), 7WT0 (human glyoxalase 1 receptor) and 8EXL (PI3K-alpha) showed outstanding binding energy and an amino acid interaction profile that stood out from the rest. The anticancer abilities of the synthesized compounds were assessed using the MTT assay, which showed that the compound 4-((2-((3-nitrobenzylidene)amino)-4-phenyl-3,4,5,6-tetrahydro-7H-cyclopenta [d]pyrimidin-7-ylidene) methyl) aniline 2a3 exhibited significant cytotoxic properties against MCF-7 cell lines. Given their highly effective performance in cellular environments, the compound 2a3, hold IC50 value of 14.03 µM/mL against MCF-7 cells and it’s a potential in the advancement of more effective treatments against cancer cell proliferation.