Abstract
Introduction:
Breast cancer (BC) treatment with conventional drugs is a medical challenge because of nonspecific targets, resistance, metastasis, and cancer relapse. Combination therapies incorporating bioactive compounds such as vitamins may enhance therapeutic efficacy and overcome these limitations. This study investigates the anticancer potential of organotin (IV) complexes in combination with vitamins D and E against key BC-associated molecular targets.
Methods:
Four organotin (IV) complexes; TBA-Ph₂ (C₂₈H₂₈O₄S₂Sn), TBA-Bu₃ (C20H36O2SSn), TBA-Bu₂ (C₂₄H₃₆O₄S₂Sn), and TBA-Me₃ (C₁₁H₁₈O₂SSn), were evaluated through molecular docking against breast cancer target proteins (AKT1, ER, EGFR, HER2, mTOR, and PI3K). Pharmacokinetic properties were predicted using SwissADME, toxicity profiles via ProTox-II, and drug-likeness through Molinspiration. The order of selected protein– ligand compounds was further analyzed using molecular dynamics simulations (CABS-flex 2.0). In vitro antioxidant activity was assessed spectrophotometrically, while antiproliferative activity was evaluated using MTT assays in MCF-7 (Estrogen-receptor positive) and MDAMB- 231 (basal-like breast cancer) cell lines.
Results:
Docking analysis revealed favorable molecular association of the organotin (IV) compound in combination with vitamins D and E, particularly against AKT1 and mTOR, accompanied by bond energies extending from −6.2 to −9.3 kcal/mol. Molecular dynamics modeling confirmed the reliability of the TBA-Bu₃–AKT1 complex. ADMET analysis indicated that TBA-Bu₃ falls under toxicity class IV, exhibiting no blood–brain barrier permeability and good gastrointestinal absorption, while vitamin E demonstrated low toxicity (class V) and favorable bioactivity. In vitro studies showed that TBA-Bu₃ exhibited potent anticancer activity against MCF-7 cells (IC₅₀ = 6.954 μM), surpassing cisplatin (IC₅₀ = 8 μM), while displaying comparatively lower antiproliferative activity in MDA-MB-231 (IC₅₀ = 16.41 μM). Additionally, TBABu₃ reduced cell survival in a dose-dependent manner and demonstrated notable antioxidant activity.
Discussion:
The potent activity of TBA-Bu₃ may be linked to its strong interactions with AKT1 and mTOR and its modulation of oxidative stress. Its enhanced effect in combination with vitamins D and E suggests a synergistic mechanism, while its selective cytotoxicity and favorable ADMET profile support its potential as a promising anticancer candidate for further studies.
Conclusion:
The findings suggest that TBA-Bu₃, particularly in combination with vitamins D and E, exhibits significant anticancer potential against MCF-7 breast cancer. Its favorable binding affinity, stability, pharmacokinetic profile, and selective cytotoxicity highlight its promise as a potential therapeutic candidate for further preclinical investigation.