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Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.

Abstract：

:Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic compounds that attracted a lot of attention because of its wide spread biological activities, the pyrrolo[1,2-a]quinoxaline heterocyclic framework has been identified as interesting scaffolds for antiproliferative activity against various human cancer cell lines. In the present study, novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives 1a-l have been designed and synthesized. Their cytotoxicities were evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines), and K562, U937, HL60 (myeloid cell lines), as well as normal human peripheral blood mononuclear cells (PBMNCs). Then, apoptosis study was performed with the more interesting compounds. The new pyrrolo[1,2-a]quinoxaline series showed promising cytotoxic potential against all leukemia cell lines tested, and some compounds showed better results than the reference compound A6730. Some compounds, such as 1a, 1e, 1g and 1h are promising because of their high activity against leukemia and their low activity against normal hematopoietic cells. Structure-activity relationships of these new synthetic compounds 1a-l are here also discussed.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Desplat V,Vincenzi M,Lucas R,Moreau S,Savrimoutou S,Pinaud N,Lesbordes J,Peyrilles E,Marchivie M,Routier S,Sonnet P,Rossi F,Ronga L,Guillon J

doi

10.1016/j.ejmech.2016.02.047

subject

Has Abstract

pub_date

2016-05-04 00:00:00

pages

214-27

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30137-4

journal_volume

113

pub_type

杂志文章

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Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.