Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution

8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild SNArH reaction between 5 and various amines. The biological evaluation indicated that methyl esters 5a are the most cytotoxic with IC50 values of 0.45 and 0.80 μM (against A549 and P388, respectively) among the parent esters 5a–5f, but 3-amino derivatives 4b and 4c of 5f with bromine showed the highest activity (with IC50 values of 0.019–0.60 μM) among the 3-amino derivatives.

Novel acenaphtho-heterocycle 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and their amino derivatives were synthesized and evaluated for their antitumor activities against cell lines of A549 and P388.Figure optionsDownload as PowerPoint slide