In Silico Study of Dibenzylidene Cyclohexanone-Based Curcumin Analogs as Potential Inhibitors of Breast Cancer Receptor Proteins

Background Cancer is one of the leading causes of death worldwide, accounting for approximately 10 million deaths annually. The most prevalent type of cancer in women is breast cancer, and there are not any prospective vaccinations available for the treatment of this disease. Objective This study aimed to identify potent substances derived from natural products, such as curcumin analogs, which are crucial for enriching drug discovery, particularly in the prevention of breast cancer. Methods This study utilized twelve novel curcumin analogs, specifically dibenzylidene-cyclohexanones, to predict their biological activity against breast cancer. Based on Lipinski's rule of five, selected compounds were screened using ADMETlab 3.0 to assess their drug-likeness properties. Then, the selected compounds were subsequently subjected to pharmacophore modeling using LigandScout, followed by molecular docking studies with the human estrogen receptor alpha (ERα; PDB ID: 2IOG) using AutoDock. Curcumin and tamoxifen were included as reference compounds for comparison. Results Based on the research conducted, all of the curcumin analogs met the criteria of Lipinski’s rule of five, except compound 12 . Compound 4 demonstrated the best potential as an anticancer agent against ERα, with a pharmacophore fit-score of 36.87 based on pharmacophore modeling and binding energy of -11.10 kcal, which was higher than tamoxifen (-10.45 kcal/mol) and curcumin (-9.18 kcal/mol) based on a molecular docking study. Conclusion Exploring curcumin analogs as potential anti-breast cancer agents is crucial for drug discovery and development. This study suggests that curcumin analog compound 4 can act as a potent inhibitor against ERα. However, further in vitro studies are required to confirm the efficacy of this compound.