706 research outputs found
Early evaluation of a new 2,2'-bipyridyl derivative with potential inhibitory activity on the ribocleotide reductase enzyme
No full text2,2'-Bipyridyl-6-carbothioamide (Bpyta) is an interesting compound, characterized by the N*-N*-S* tridentate ligand system [1]. It demonstrated in vitro antitumoral activity much higher than hydroxyurea (Hu) on murine and tumoral lines and on human acute leukemias; it seems to be active on the key enzyme ribonucleotide reductase (RR), M2 subunit [2]. In order to verify if the introduction of another carbothioamidic group in 6' position of Bpyta can potentiate antitumor activity of this compound, 2,2'-Bypyridyl-6,6'-dicarbothioamide (Bpy-dita) was synthesized.
We evaluate cytotoxic activity of the new molecule on a panel of tumoral cell lines (P388, C-26, B16, CHO and HL-60) by using an antimetabolic assay. Bpy-dita was found more potent than 10 times with respect to Bpyta and more than 100 times with respect to Hu. Bpy-dita concentration resulting in 50% inhibition of radioisotope incorporation ranged between 72 and 610 nM. The compound was insoluble in water and was dissolved in Dimethyl sulfoxide (DMSO) until a concentration of 2 mM and in a solution 25% polyethylene glycol (Peg) until a concentration of 0.1 mM. Final concentration of DMSO and Peg did not have any cytotoxic effect on our testing systems.
Such a result suggests Bpy-dita is a highly cytotoxic compound. To evaluate its mechanism of action we are going to test its inhibitory activity on RR.
[1] Antonini, I et al 1981, J Med Chem 24, 1181.
[2] Nocentini G et al 1990, Proc XI Int Congress of Pharmacology, Amsterda
Gli straordinari progressi dei trattamenti anti-retrovirali e il nuovo profilo del paziente con HIV
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