title: Synthesis and Antiproliferative Effect of Ethyl 4-[4-(4-Substituted Piperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxalinecarboxylate Derivatives on Human Leukemia Cells.
abstract: 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 us to look for new specific molecules for leukemia subtypes or for therapy-resistant cases. Among heterocyclic derivatives that attracted attention due to their wide range of biological activities, we focused our interest on 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-substituted piperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxalinecarboxylate derivatives (1 a-o) were designed, synthesized, and evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines) and K562, U937, and HL60 (myeloid cell lines), as well as on normal human peripheral blood mononuclear cells (PBMCs). This new pyrrolo[1,2-a]quinoxaline series showed interesting cytotoxic potential against all tested leukemia cell lines. In particular, pyrroloquinoxalines 1 a and 1 m,n seem to be interesting due to their high activity against leukemia and their low activity against normal hematopoietic cells, leading to a high index of selectivity.
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, 33076, Bordeaux cedex, France.|INSERM U1035, Cellules souches hématopoïétiques normales et leucémiques, 33000, Bordeaux, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Desplat
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.|Department of Pharmacy and CIRPeB, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Marian
authors.initials: M
authors.lastname: Vincenzi
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Lucas
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Moreau
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Savrimoutou
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rubio
authors.affiliation: ISM-CNRS UMR 5255, Univ. Bordeaux, 351 cours de la Libération, 33405, Talence cedex, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Pinaud
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: David
authors.initials: D
authors.lastname: Bigat
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Enriquez
authors.affiliation: ICMCB CNRS-UPR 9048, Univ. Bordeaux, 87 Avenue du Docteur Schweitzer, 33608, Pessac cedex, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Marchivie
authors.affiliation: Institut de Chimie Organique et analytique, Univ. Orleans, CNRS UMR 7311, ICOA, BP 6759, rue de Chartres, 45067, Orléans cedex 2, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Routier
authors.affiliation: Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, UMR CNRS 7378, UFR de Pharmacie, Université de Picardie Jules Verne, 1 rue des Louvels, 80037, Amiens cedex 01, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
authors.affiliation: Department of Pharmacy and CIRPeB, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronga
authors.affiliation: UFR des Sciences Pharmaceutiques, Univ. Bordeaux, ARNA Laboratory, 33076, Bordeaux cedex, France.|INSERM U1212, UMR CNRS 5320, ARNA Laboratory, 33000, Bordeaux, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology*; D008958:Models, Molecular; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011810:Quinoxalines
keywords: anticancer agents; cytotoxic activity; leukemia; pyrrolo[1,2-a]quinoxalines; synthesis