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Abstract <p>In this study, a novel platinum(II) coordination complex, Pt(HX)<sub>2</sub>Cl<sub>2</sub>, incorporating hypoxanthine ligands, was synthesized and fully characterized using Fourier-transform infrared (FTIR), <sup>1</sup>H/<sup>13</sup>C 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 IC<sub>50</sub> value of 56.67 µg/mL. Although less aggressive than cisplatin (IC<sub>50</sub> = 20.0 µg/mL) at lower doses, Pt(HX)<sub>2</sub>Cl<sub>2</sub> 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)<sub>2</sub>Cl<sub>2</sub> as a promising, safer alternative to classical platinum-based chemotherapeutics with a distinct apoptosis-inducing mechanism.</p>

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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

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Ç. Bilkan

摘要

Abstract

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.