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 S_NAr^H 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.