http://hdl.handle.net/10256/1535 2025-10-09T07:46:19Z 2025-10-09T07:46:19Z Gonzalo-Navarro, Carlos Troyano Saez, Antonio J. García-Béjar Bermejo, Beatriz Bermejo Organero Gallego, Juan Ángel Massaguer i Vall-llovera, Anna Santos Peinado, Lucía Rodríguez Fernández-Pacheco, Ana María Manzano, Blanca R. Durá, Gema http://hdl.handle.net/10256/27503 2025-10-08T06:46:04Z 2024-11-01T00:00:00Z

Ru-terpyridine complexes containing clotrimazole as potent photoactivatable selective antifungal agents Gonzalo-Navarro, Carlos; Troyano Saez, Antonio J.; García-Béjar Bermejo, Beatriz Bermejo; Organero Gallego, Juan Ángel; Massaguer i Vall-llovera, Anna; Santos Peinado, Lucía; Rodríguez Fernández-Pacheco, Ana María; Manzano, Blanca R.; Durá, Gema The overuse of antimicrobial agents in medical and veterinary applications has led to the development of antimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. In this context, the use of transition metal complexes with photoactivatable properties, which can act as drug delivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In this work several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycotic drug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes as antifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. The complexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period of time. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT calculations. The complexes were tested against three different yeasts, which were selected based on their prevalence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligand showed the best activity against the three species under light, with minimal inhibitory concentration values of 0.88 μM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that of free clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were more active on yeast species than on cancer cell lines

2024-11-01T00:00:00Z Veiga del Pino, José Manuel Scalambra, Franco Bermejo-Casadesus, Cristina Massaguer i Vall-llovera, Anna García Maroto, Federico Romerosa Nievas, Antonio Manuel http://hdl.handle.net/10256/27502 2025-10-08T06:13:04Z 2023-09-01T00:00:00Z

Study of the biological activity of photoactive bipyridyl-Ru(II) complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA) Veiga del Pino, José Manuel; Scalambra, Franco; Bermejo-Casadesus, Cristina; Massaguer i Vall-llovera, Anna; García Maroto, Federico; Romerosa Nievas, Antonio Manuel The water-soluble ruthenium complex cis-[Ru(dcbpyH)2(PTAH)2]Cl2·3H2O (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine; PTA = 1,3,5-triaza-7-phosphaadamantane) has been synthesized and characterised by NMR, IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The optical properties of 1 were studied, including photoactivation under visible light, as well as its biological properties, together with those of the previously published Ru complexes cis-[Ru(bpy)2(PTA)2]Cl2 (2), trans-[Ru(bpy)2(PTA)2](CF3SO3)2 (3) and cis-[Ru(bpy)2(H2O)(PTA)](CF3SO3)2 (4) (bpy = 2,2'-bipyridine). Anticancer activities of the complexes against human lung (A549), cervical (HeLa) and prostate (PC3) carcinoma cells were evaluated under dark conditions and upon photoactivation with visible light. None of the complexes exhibited cytotoxic activity in the absence of light irradiation (IC50 > 100 μM). However, after photoactivation, the cytotoxicity of complexes 1, 2 and 3 against the three cell lines markedly increased, resulting in IC50 values between 25.3 μM and 9.3 μM. Notably, these complexes did not show toxicity against red blood cells. These findings show the potential of complexes 1, 2 and, particularly, 3 for selective and controlled cancer photochemotherapy. The reactivity of the Ru complexes against DNA under UV-Vis irradiation was studied by analysing plasmid mobility. Experimental data shows that 4 unfolds supercoiled DNA (SC DNA) both in the dark and under visible irradiation, while 1 and 3 are only active under light, being 2 inactive in either case. The unfolding activities of complexes 3 and 4 were dependent on the air present in the reaction. The measured intracellular levels of reactive oxygen species (ROS) upon irradiation with complexes 1, 2 and 3 suggest that their mechanism of action is related to oxidative stress

2023-09-01T00:00:00Z Echevarría Poza, Igor Zafon, Elisenda Barrabés Vera, Sílvia Martínez, María Ángeles Ramos Gómez, Sonia Ortega Santamaría, Natividad Manzano, Blanca R. Jalón, Félix A. Quesada Pato, Roberto Espino Ordóñez, Gustavo Massaguer i Vall-llovera, Anna http://hdl.handle.net/10256/27498 2025-10-07T10:55:47Z 2022-06-01T00:00:00Z

Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer Echevarría Poza, Igor; Zafon, Elisenda; Barrabés Vera, Sílvia; Martínez, María Ángeles; Ramos Gómez, Sonia; Ortega Santamaría, Natividad; Manzano, Blanca R.; Jalón, Félix A.; Quesada Pato, Roberto; Espino Ordóñez, Gustavo; Massaguer i Vall-llovera, Anna Despite their outstanding properties as potential photosensitizers for photodynamic therapy (PDT), Ir(III) biscyclometalated complexes need both further developments to overcome remaining limitations and in-depth investigations into their mechanisms of action to reach clinic application in the treatment of cancer. This work describes the synthesis of a family of Ir(III) complexes of general formula [Ir(C^N)2(N^N′)]Cl (N^N′ = thiabendazole-based ligands; C^N = ppy (2-phenylpyridinate) (Series A), or dfppy (2-(2,4-difluorophenyl)pyridinate) (Series B)) and their evaluation as potential PDT agents. These complexes are partially soluble in water and exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, the cytotoxic activity of derivatives of Series A is enhanced upon irradiation, particularly for complexes [1a]Cl and [3a]Cl, which show phototoxicity indexes (PI) above 20. Endocytosis was established as the uptake mechanism for [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in the mitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Cl induce death on cancer cells under irradiation through apoptosis triggered by a multimodal mechanism of action, which likely involves damage over mitochondrial DNA and mitochondrial membrane depolarization. Both processes seem to be the result of photocatalytic oxidation processes.

2022-06-01T00:00:00Z Gonzalo-Navarro, Carlos Zafon, Elisenda Organero Gallego, Juan Ángel Jalón, Félix A. Lima, Joao Carlos Espino Ordóñez, Gustavo Rodríguez, Ana María Blanco Santos Peinado, Lucía Moro, Artut J. Barrabés Vera, Sílvia Castro Gallegos, Jessica Camacho-Aguayo, Javier Massaguer i Vall-llovera, Anna Manzano, Blanca R. Durá, Gema http://hdl.handle.net/10256/27496 2025-10-08T06:33:00Z 2024-01-30T00:00:00Z

Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy Gonzalo-Navarro, Carlos; Zafon, Elisenda; Organero Gallego, Juan Ángel; Jalón, Félix A.; Lima, Joao Carlos; Espino Ordóñez, Gustavo; Rodríguez, Ana María Blanco; Santos Peinado, Lucía; Moro, Artut J.; Barrabés Vera, Sílvia; Castro Gallegos, Jessica; Camacho-Aguayo, Javier; Massaguer i Vall-llovera, Anna; Manzano, Blanca R.; Durá, Gema One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT

2024-01-30T00:00:00Z