In Silico Study of Indole–Tetrazole Hybrid Derivatives as Potential Breast Cancer Anticancer Candidates Through Molecular Docking Against HER2, ADMET Profile Prediction, and Drug-Likeness Assessment

Breast cancer remains one of the leading causes of mortality among women worldwide, highlighting the urgent need for the development of more effective therapeutic agents with fewer adverse effects. This study aimed to analyze the potential of indole–tetrazole hybrid derivatives as anti-breast cancer agents by comparing their performance with the reference compound Bazedoxifen. The design of indole–tetrazole hybrid compounds, which integrates two pharmacologically active moieties within a single molecular framework, is expected to enhance biological activity and strengthen interactions with target proteins. The methods employed in this study included molecular docking to evaluate ligand binding affinity to the HER2 protein (PDB ID: 7PCD), Lipinski’s Rule of Five analysis to assess drug-likeness for oral administration, and ADMET prediction to evaluate pharmacokinetic and toxicity profiles. SwissADME and pkCSM were used to assess the drug-likeness of the compounds based on Lipinski’s Rule of Five and to predict their ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. The key parameters analyzed in the docking study were binding affinity (ΔG), root mean square deviation (RMSD), and the types of interactions with amino acid residues at the active site. The results indicated that most compounds satisfied Lipinski’s criteria and exhibited good absorption profiles, as well as non-mutagenic properties based on Ames test predictions. Compound 10 exhibited the best binding affinity (−13.0444 kcal/mol) and showed interactions with key amino acid residues, indicating a stable ligand–protein complex. Overall, compound 10 was identified as the most promising candidate for further development as an anti-breast cancer agent. However, further experimental validation through both in vitro and in vivo studies is required to confirm the compound's pharmacological potential and safety profile before it can be considered for drug development.