RESUMEN
N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer.
Asunto(s)
Antineoplásicos , Carbazoles , Diseño de Fármacos , Compuestos Heterocíclicos , Metano , Carbazoles/química , Carbazoles/farmacología , Carbazoles/síntesis química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis química , Relación Estructura-Actividad , Metano/análogos & derivados , Metano/química , Metano/farmacología , Estructura Molecular , Oro/química , Oro/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Animales , Relación Dosis-Respuesta a Droga , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/síntesis químicaRESUMEN
The aim of the present study was to investigate the in vitro antioxidant and antitumor effects of Salvia fruticosa Mill subsp. thomasii (Lacaita) Brullo, Guglielmo, Pavone & Terrasi (Lamiaceae). The aerial parts were extracted by maceration with methanol. This extract was partitioned with methanol and n-hexane. Luteolin, luteolin 7-O-glucoside, rutin and salvigenin were isolated from the methanol-soluble fraction. n-Hexane fraction showed viridiflorol, ß-pinene, 1,8-cineole, as main components. The methanol-soluble fraction exerted antitumor activity against human breast cancer (MCF-7 and MDA-MB-231) and human colorectal carcinoma (RKO and Caco-2) cells. TUNEL test revealed that S. fruticosa subsp. thomasii leads to cells death by apoptosis, with low cytotoxic effects on non-tumoral 3T3-L1 cells. Moreover, it exerted the highest protection of lipid peroxidation and reduced the oxidative stress induced by menadione treatment in 3T3-L1 murine fibroblasts. S. fruticosa subsp. thomasii bioactivity could promote its use not only as food but also in nutraceutical/pharmaceutical industries.