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  3. Exploring Gallium(III) Complexes as Emerging Therapeutic Candidates for Breast Cancer

Exploring Gallium(III) Complexes as Emerging Therapeutic Candidates for Breast Cancer

  • J Med Chem. 2026 Apr 23;69(8):9051-9070. doi: 10.1021/acs.jmedchem.5c03480.
Alberto Moreno-Fernández 1,  Elena Domínguez-Jurado 2,  Marc Martínez de Sarasa Buchaca 1,  Sofía Blas 2,  María Del Mar Noblejas-López 2,  Carmen Moya 2,  Fernando de Andrés 3 4,  Iván Bravo 2,  Jose-Daniel Aroca-Aguilar 5,  Jesús-José Ferre-Fernández 5,  Julio Escribano 5,  Antonio Rodríguez-Diéguez 6,  Pablo Salcedo-Abraira 6,  Santiago García-Yuste 1,  Carlos Alonso-Moreno 2,  Agustín Lara-Sánchez 1
Affiliations

Affiliations

  • 1 Universidad de Castilla-La Mancha, Departamento de Química Inorgánica, Orgánica y Bioquímica-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Ciencias y Tecnologías Químicas, Instituto Regional de Investigación Científica Aplicada-IRICA, 13071 Ciudad Real, Spain.
  • 2 Universidad de Castilla-La Mancha, Departamento de Química Inorgánica, Orgánica y Bioquímica-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Unidad NanoDrug, Facultad de Farmacia, 02071 Albacete, Spain.
  • 3 Universidad de Castilla-La Mancha, Departamento de Química Analítica y Tecnología de Alimentos, Facultad de Farmacia de Albacete, 02071 Albacete, Spain.
  • 4 Universidad de Castilla-La Mancha, Instituto Regional de Investigación Científica Aplicada IRICA, 13005 Ciudad Real, Spain.
  • 5 Universidad de Castilla-La Mancha, Genetics, Castilla-La Mancha University Medical School, 02008 Albacete, Spain.
  • 6 Universidad de Granada, Departamento de Química Inorgánica, Facultad de Ciencias, 18071 Granada, Spain.
PMID: 41940724 DOI: 10.1021/acs.jmedchem.5c03480
Abstract

Despite the clinical success of platinum chemotherapeutics, severe side effects and resistance drive the search for alternative metallodrugs. Gallium compounds are promising due to their ability to mimic iron(III) and disrupt essential cellular processes; however, poor aqueous stability and moderate cytotoxicity have limited their development. Herein, we report a new family of heteroscorpionate gallium(III) salts, [Ga(κ3-NNO)2][GaCl4] (Ga1-Ga6). NMR spectroscopy and single-crystal X-ray diffraction confirmed their molecular structures. The complexes exhibit remarkable air and Moisture stability, with tunable lipophilicity and solubility governed by ligand electronics. Ga3 and Ga6, bearing dimethylamino substituents, showed nanomolar cytotoxicity across breast Cancer cell lines, outperforming classical platinum drugs. The lead compound Ga6 displayed high hydrolytic stability, selective tumor-cell uptake, cytoplasmic localization, and significant tumor growth inhibition in zebrafish xenografts without observable systemic toxicity in mice, underscoring the potential of the heteroscorpionate platform.

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