RESUMEN
The present study aimed to determine the chemical composition, antioxidant effects and antitumor properties of a methanol extract of Anchusa azurea Mill. (Boraginaceae) aerial parts against four tumour cell lines (MCF-7, MDA-MB-231, RKO, and R2C). The antioxidant effects were assessed by using ß-carotene bleaching, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing ability power (FRAP) tests. HPLC analyses revealed chlorogenic acid, catechin, caffeic acid, and astragalin as the most abundant compounds. Interesting results were obtained in the ß-carotene bleaching test with IC50 values of 7.6 and 27.5 µg mL-1 after 30 and 60 min of incubation, respectively. Furthermore, the A. azurea extract protects 3T3-L1 mouse cells from oxidative stress induced by menadione and exhibits good antitumor activity, with very low toxicity. Our data indicate that the antitumor properties are due to the ability to induce programmed cancer cell death through caspase 3/7 and 9 activation and interference with the cytoskeleton dynamics.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Boraginaceae/química , Citoesqueleto/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacología , Animales , Antioxidantes/farmacología , Benzotiazoles , Compuestos de Bifenilo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ratones , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/química , Fitoquímicos/farmacología , Picratos , Especies Reactivas de Oxígeno , Ácidos SulfónicosRESUMEN
In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer's disease.