In silico exploration of diboronocurcumin analogs as anti-breast cancer agents using integrative bioinformatics and molecular docking

Context: The development of curcumin analog compounds containing boron as anticancer agents is ongoing. Diboronocurcumin analogs are promising for development as selective and targeted anti-breast cancer agents. We designed five novel diboronocurcumin analogs (CCB-4 to CCB-8) featuring heterocyclic ketones to address current limitations in breast cancer treatment, including resistance and toxicity. Aims: To identify potential targets and molecular pathways of diboronocurcumin analogs in breast cancer, utilizing a bioinformatics technique and structure-based in silico research. Methods: Target prediction was performed using databases including TargetNet, GeneCards, OMIM, and NCBI. Functional network analysis tools, such as STRING, Cytoscape, GO, and KEGG, were utilized to identify key signaling pathways in breast cancer. Molecular docking was employed to evaluate the binding interactions between diboronocurcumin analogs and the predicted target proteins. Results: ESR1, RELA, HDAC1, and MMP9 were four targets of diboronocurcumin analogs implicated in the processes of breast cancer cell proliferation, metastasis, and death, according to bioinformatics approaches. Molecular docking studies revealed that diboronocurcumin analogs had a high affinity for the four targets. CCB-4 to CCB-8 demonstrated stronger binding to ESR1 (-10.18, -10.49, -9.19, -10.24, and -10.85 kcal/mol, respectively) than tamoxifen (-9.52 kcal/mol). In addition, CCB-5 and CCB-8 exhibited greater binding to IKK (upstream pathway kinase of RELA), compared to doxorubicin, tamoxifen, and lapatinib. Conclusions: This study provides insights into the multi-target potential of diboronocurcumin analogs in suppressing breast cancer progression. Further in vitro and in vivo validation is supported by encouraging in silico results, particularly for CCB-5 and CCB-8.