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Mitochondria-Targeted Benzoxazole-Based Platinum Photosensitizer Complexes: Photophysical Properties and Photocytotoxicity Evaluation Against Breast and Gastric Cancer Cells.

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Journal of medicinal chemistry 📖 저널 OA 13.8% 2023: 1/1 OA 2024: 1/8 OA 2025: 14/81 OA 2026: 14/134 OA 2023~2026 2025 Vol.68(16) p. 17065-17086
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Rabor JT, Mandegani Z, Aboonajmi J, Rastegari B, Niroomand Hosseini F, Meurer F, Bodensteiner M, Hoseini SJ, Nabavizadeh SM

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This study explores platinum(II) phototherapy using cycloplatinated compounds with bidentate 2-(4-substituted) benzoxazole ligands, [Pt()()()] ().

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APA Rabor JT, Mandegani Z, et al. (2025). Mitochondria-Targeted Benzoxazole-Based Platinum Photosensitizer Complexes: Photophysical Properties and Photocytotoxicity Evaluation Against Breast and Gastric Cancer Cells.. Journal of medicinal chemistry, 68(16), 17065-17086. https://doi.org/10.1021/acs.jmedchem.5c00543
MLA Rabor JT, et al.. "Mitochondria-Targeted Benzoxazole-Based Platinum Photosensitizer Complexes: Photophysical Properties and Photocytotoxicity Evaluation Against Breast and Gastric Cancer Cells.." Journal of medicinal chemistry, vol. 68, no. 16, 2025, pp. 17065-17086.
PMID 40785274 ↗

Abstract

This study explores platinum(II) phototherapy using cycloplatinated compounds with bidentate 2-(4-substituted) benzoxazole ligands, [Pt()()()] (). The compounds were synthesized and fully characterized, and their photophysical, cytotoxic, and phototoxic properties were analyzed. Time-dependent Density Functional Theory (TD-DFT) calculations supported the analysis of the complexes absorption and photoluminescence, with high-energy absorption showing L'LCT/MLCT [π(Cl, Me) → π*(C^N)] contributions. Among the complexes, ( = C^N, = κ--C^N, = Cl) exhibited the highest quantum yield (Φ = 48%) and showed strong antiproliferative activity in breast carcinoma (MCF-7) and gastric adenocarcinoma (AGS) cell lines. (, = N^N, = Cl, = Cl, , = N^N, = Me, = Me; , = C^N, = DMSO, = Cl; , = C^N, = C^N, = Cl, and , = C^N, = Me, = DMSO) also demonstrated potential as photoactivatable agents. Mechanistic studies indicated that the complexes triggered ROS generation, mitochondrial dysfunction, and lysosomal damage, with showing promise for photochemotherapeutic treatment of gastric and breast cancer due to its selectivity and effectiveness in targeting mitochondria and lysosomes.

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