Iminophosphine ligands find extensive applications in homogeneous catalysis; however, their potential antitumor activity is currently being explored. Including biologically active moieties, such as aminoalcohols, could enhance this activity further. Therefore, we have synthesised a novel series of Pd(II) and Pt(II) iminophosphine complexes incorporating aminoalcohols as biologically active moieties to explore the potential of enhancing this activity. The series of Pd(II) complexes includes complexes 2a, 2f, and 2h, which were previously reported by our research group as catalysts in Suzuki–Miyaura cross-coupling reaction in aqueous media. Besides their complete characterisation, some structures have been unequivocally corroborated by single-crystal X-ray diffraction (SC-XRD). To evaluate the cytotoxic potential of the complexes, a preliminary in vitro study was conducted on different cancerous cell lines, including using COS-7 cells as a healthy cell line. Notably, complexes 2e, 2f, and 3b exhibited selectivity towards human chronic myelogenous leukaemia (K562), demonstrating IC₅₀ values of 7.73 ± 1.4 µM, 8.53 ± 1.9 µM, and 8.83 ± 1.5 µM, respectively. Remarkably, the selectivity of these complexes surpassed that of cisplatin. Furthermore, in silico analysis indicated a higher binding energy of these complexes to DNA when compared to cisplatin.

Background/Objectives: The development of new metallodrugs has represented an important milestone in recent years for their potential application in different therapeutic approaches. Therefore, the objective of this study was to synthesize a series of P^N iminophosphine Pd(II) complexes (1Pd–3Pd) incorporating different aliphatic amines. Methods: All complexes were characterized using several spectroscopic and analytical techniques, including ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopy, mass spectrometry, FT-IR spectroscopy, and elemental analysis. In addition, complex 3Pd was unambiguously characterized by single-crystal X-ray diffraction. Results: Supramolecular studies allowed the main noncovalent interactions responsible for stabilizing the crystal lattice of complex 3Pd to be identified. These interactions were analyzed using Hirshfeld surface analysis, which revealed that C-H···π and C-H···Cl interactions contributed most significantly to the stabilization of the crystal lattice. All complexes exhibited stability in different solvents and positive lipophilicity values, with complex 3Pd displaying the highest hydrophobicity. Through in vitro studies, the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of all complexes were determined against different Gram-positive and Gram-negative bacterial strains, as well as fungal strains of Candida species. Complex 3Pd exhibited the highest activity, particularly against L. monocytogenes (1.17 µg/mL), P. aeruginosa (4.68 µg/mL), and all fungal strains (18.75 µg/mL), displaying both bactericidal and fungicidal activity. Furthermore, in silico studies enabled the identification of the potential modes of action of the complexes against different molecular targets present in the bacterial and fungal strains. Conclusions: These results demonstrate the efficacy of the three synthesized complexes against different virulent strains exhibiting resistance to broad-spectrum drugs. Furthermore, the presence of the metal center, together with the incorporation of increasingly longer aliphatic chains, appears to enhance the antibacterial and antifungal activity of the complexes.

Este artículo de revisión aborda la evolución de los antibióticos y las estrategias actuales para enfrentar la resistencia bacteriana. Se sitúa el tema desde el uso histórico de sustancias antimicrobianas hasta la consolidación del concepto moderno de antibiótico. Se describe su clasificación por estructura y por mecanismo de acción, haciendo énfasis en blancos esenciales: pared celular, síntesis de ácidos nucleicos, vías metabólicas y síntesis de proteínas. Se revisan brevemente los mecanismos de resistencia intrínseca, adquirida y adaptativa, como modificaciones del blanco, reducción de permeabilidad, bombas de eflujo, inactivación enzimática y biofilms. Finalmente, se compendian investigaciones donde antibióticos convencionales se coordinan con centros metálicos (p. ej., Cu(II), Zn(II), Co(II), Ni(II), entre otros), con el objetivo de mejorar solubilidad, estabilidad y, en algunos casos, potenciar la actividad frente a bacterias Gram positivas y negativas. En conjunto, estos enfoques buscan reposicionar fármacos conocidos mediante química de coordinación y formulación avanzada, con evaluación rigurosa de eficacia. DOI: https://doi.org/10.54167/tch.v20i1.2312