Synthesis and antiproliferative effect of new ethyl 4-(4-substitutedpiperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives on human leukemic cells

Acute leukemia is a hematological malignancy with high incidence and recurrence rates, and is characterized by an accumulation of blasts in bone marrow due to proliferation of immature lymphoid or myeloid cells associated with a blockade of differentiation. The heterogeneity of leukemia led to look for new specific molecules for leukemia subtypes or even for therapyresistant cases. Among heterocyclic derivatives that attracted attention due to their large spread biological activities, we have focused our interest towards the pyrrolo[1,2-a]quinoxaline heterocyclic framework that has been previously identified as an interesting scaffold for antiproliferative activities against various human cancer cell lines. In this work, new ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives 1a-o have been designed, synthesized and evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines), and K562, U937, HL60 (myeloid cell lines), and also on normal human peripheral blood mononuclear cells (PBMNCs). These new pyrrolo[1,2-a]quinoxaline series showed interesting cytotoxic potential against all tested leukemia cell lines. In particular, pyrroloquinoxalines 1a and 1m-n seem to be interesting due to their high ctivity against leukemia and their low activity against normal hematopoietic cells leading to high index of selectivity.