Design and synthesis of modulators of apoptotic activity

p53 is a transcription factor with tumour suppressor properties, which is able to induce mitochondrial apoptosis independently of its transcriptional activity. Analogues of the spiro[imidazo[1,5-c] thiazole-3,3-indoline] -2,5,7(6H,7aH) -trione, previously synthesized from my research group, as p53 modulators were synthesized during my PhD, aiming to explore new structural requirements at the thiazolidine domain to increase the antiproliferative activity and improve p53 modulation. Derivative 5-bromo-3- (cyclohexane carbonyl) -1-methyl-2oxospiro[indoline-3,2-thiazolidine] (SM13) emerged as the most potent compound of all series, inhibiting, in vitro, 30% of p53MDM2 interaction at 5 M and the cell growth of different human tumor cells at nanomolar concentrations... [edited by author]