Synthesis, Spectroscopic Characterization, Computational Studies and In Vitro Anticancer Investigations of a Novel Platinum(II)–Hypoxanthine Complex: Targeting ERα and Inducing Apoptosis in MCF-7 Cells

In this study, a novel platinum(II) coordination complex, Pt(HX)₂Cl₂, incorporating hypoxanthine ligands, was synthesized and fully characterized using Fourier-transform infrared (FTIR), ¹H/¹³C nuclear magnetic resonance (NMR) spectroscopy, and density functional theory (DFT) calculations. Spectroscopic data confirmed that coordination occurs via the N7 nitrogen atoms of the ligand in a distorted square-planar geometry. The anticancer potential of the complex was evaluated against ERα-positive MCF‑7 breast cancer cells and compared with cisplatin and tamoxifen. The complex exhibited a dose-dependent antiproliferative activity with an IC₅₀ value of 56.67 µg/mL. Although less aggressive than cisplatin (IC₅₀ = 20.0 µg/mL) at lower doses, Pt(HX)₂Cl₂ achieved comparable efficacy at therapeutic concentrations (reducing viability to 28% at 75 µg/mL). Crucially, flow cytometric analysis revealed that the compound induces cell death primarily via apoptosis (34.9%) rather than necrosis, matching the apoptotic efficacy of cisplatin (36.9%) and tamoxifen (39.2%). Molecular docking simulations indicated that the complex acts as a high-affinity dual-targeting agent, exhibiting a superior binding score (–107.06) against the estrogen receptor alpha (ERα) compared to the reference drugs. Furthermore, in silico ADMET and toxicity assessments predicted a significantly improved safety profile, characterized by lower systemic toxicity (Class 4), reduced risks of hepatotoxicity and neurotoxicity, and minimal blood-brain barrier penetration. Collectively, these findings highlight Pt(HX)₂Cl₂ as a promising, safer alternative to classical platinum-based chemotherapeutics with a distinct apoptosis-inducing mechanism.