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

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 (96 visite)

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

Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 1768-3254electronic), 2016; 113: 214-227.

Tipo di articolo: Journal Article,

Impact factor: 4.519, Impact factor a 5 anni: 4.187

Url: https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84959375519&partnerID=40&md5=1dea32a36b6c88eafc5d9f6d11e862df

Parole chiave: Cancer, Cytotoxic Activity, Leukemia, Pyrrolo[1, 2-A]quinoxaline, Synthesis,

Affiliazioni:

*** IBB - CNR ***
Univ. Bordeaux, UFR des Sciences Pharmaceutiques, Cellules Souches Hematopoietiques Normales et Leucemiques, Bordeaux cedex, France
INSERM U1035, Cellules Souches Hématopoïétiques Normales et Leucémiques, Bordeaux, France
INSERM U1212, UMR, CNRS 5320, ARNA Laboratory, Bordeaux, France
Department of Pharmacy, CIRPeB, University of Naples Federico II, Via Mezzocannone, Naples, Italy
Univ. Bordeaux, ISM, CNRS, UMR 5255, 351 cours de la Libération, Talence cedex, France
Univ. Bordeaux, ICMCB, CNRS, UPR 9048, 87, Avenue du Docteur Schweitzer, Pessac cedex, France
Institut de Chimie Organique et Analytique, Univ. Orleans, CNRS, UMR 7311, ICOA, BP 6759, rue de Chartres, Orléans cedex 2, France
Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, UMR, CNRS 7378, UFR de Pharmacie, 1 rue des Louvels, Amiens cedex 01, France

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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. © 2016 Elsevier Masson SAS. All rights reserved.

▼ Test e validazione di nuove sonde molecolari mediante imaging preclinico.