Molecular docking and pharmacokinetic evaluations of curcumin-based scaffolds as MDM2-p53 inhibitors

Cancer is a disease that is considered one of the worst in the world, and as a result, researchers are constantly looking for natural remedies to alleviate the negative effects of conventional cancer therapy. p53, a tumor suppressor protein, and its inhibitor, MDM2, an oncogenic protein, are becoming increasingly important in cancer therapy. Computational drug discovery is a valuable tool in identifying targets, determining structure–activity relationships, calculating binding affinity through molecular docking, conducting molecular dynamics simulations, and profiling targeted protein and ligand complexes in cancer therapy. Among the curcumin congeners studied (43 substructure), C21 and C22 exhibited the highest binding affinity of − 7.7 kcal/mol and − 7.3 kcal/mol, respectively. Compounds C21 and C22 exhibited favourable pharmacokinetic properties. The stability of the protein–ligand complex was investigated using the imods server, which considers the higher flexibility of the complexes. Normal mode analysis established the stability of the protein–ligand complex. Moreover, the chosen compound's ADME profiles suggest a strong response, making it a promising lead molecule. However, it is crucial to synthesize the recommended chemicals and assess their effectiveness using in vitro and in vivo tests.