Translational medicine: preclinical development and optimization of new antitumor agents

GIOLITO MV; BOGGIÁN, D; MATA E; DELPICCOLO, C.; OG SCHAROVSKY; M. J. RICO; CORNIER P; L. E. MAINETTI; ROZADOS V

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXIV Reunión Anual de la Sociedad Argentina de Inmunología, XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental.; 2016

SAIC-SAI-SAFE

The development of new antitumor agents is, presently, a demand for the public health due to the demonstrated side effects of the known antineoplastic drugs, to the development of drug resistance and, also, to the lack of effective therapies for some types of cancer and for the treatment of metastasis. The purpose of this study was to evaluate the antitumor activity of the synthesised compounds (aminoacyl/peptidyl penicilines, dihidroisocumarines, propagilamines, stilbenes, β-lactamase and oxadiazoles) and their mechanisms of action. The inhibition of the proliferation, measured with the tetrazolium salt WST-1 reagent, of the murine 4T1 mammary carcinoma cell line was evaluated by incubating them for 48 h with RPMI medium+10%FBS in the presence of decreasing concentrations (100 to 10 µM) of the compounds. According to the obtained results, there were chosen 6/44 compounds: 22i, 266, 171, 4210, 3151 and 6, which have shown antiproliferative effect, of, at least, 50% with respect to the control, at the lowest doses (25 and 10 µM). It was evaluated the migratory capacity by scratch-wound assays of 4T1 cells in the presence of the chosen compounds. Compared to the control group without treatment, 4T1 cells showed a lower migratory capacity when cultured during 4 h with 22i compound (P