Ru-terpyridine complexes containing clotrimazole as potent photoactivatable selective antifungal agents

The overuse of antimicrobial agents in medical and veterinary applications has led to the development ofantimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. Inthis context, the use of transition metal complexes with photoactivatable properties,...

Descripción completa

Detalles Bibliográficos
Autores: Gonzalo Navarro, Carlos, Troyano Saez, Antonio J, García-Béjar Bermejo, Beatriz, Massaguer , Anna, Organero Gallego, Juan Ángel, Santos Peinado, Lucía, Rodríguez Fernández-Pacheco, Ana María, Manzano Manrique, Blanca Rosa Lourdes, Durá Gracia, Gema
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/39446
Acceso en línea:https://www.sciencedirect.com/science/article/pii/S0162013424002162?via%3Dihub
https://hdl.handle.net/10578/39446
Access Level:acceso abierto
Palabra clave:Antifungal ruthenium complexes
Antimicrobial
Clotrimazole
PhotoActivated therapy PACT
Photodissociation
Substituted terpyridine ligands
Descripción
Sumario:The overuse of antimicrobial agents in medical and veterinary applications has led to the development ofantimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. Inthis context, the use of transition metal complexes with photoactivatable properties, which can act as drugdelivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In thiswork several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycoticdrug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes asantifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. Thecomplexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period oftime. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT cal-culations. The complexes were tested against three different yeasts, which were selected based on their preva-lence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligandshowed the best activity against the three species under light, with minimal inhibitory concentration values of0.88 µM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that offree clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were moreactive on yeast species than on cancer cell lines.