title: Synthesis and biological activity of ferrocenyl indeno[1,2-c]isoquinolines as topoisomerase II inhibitors.
abstract: Three series of indeno[1,2-c]isoquinolines bearing a ferrocenyl entity were synthesized and evaluated for DNA interaction, topoisomerase I and II inhibition, and cytotoxicity against breast human cancer cell lines. In the first and second series, the ferrocenyl scaffold was inserted as a linker between the two nitrogen atoms. In the last series, it was introduced at the end of the carbon chain. The present study showed that the ferrocenyl entity enhanced the topoisomerase II inhibition. Most compounds showed a potent growth inhibitory effect on MDA-MB-231 cell line with the IC50 in μM range.
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France; Univ. Yaoundé 1, Laboratoire de Chimie de Coordination, BP 812, Yaoundé, Cameroon.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wambang
authors.affiliation: Univ. Lille, CHU Lille, EA 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Schifano-Faux
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Aillerie
authors.affiliation: Univ. Lille, Inserm, U908-CPAC-Cell Plasticity and Cancer, F-59000 Lille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Baldeyrou
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Jacquet
authors.affiliation: Univ. Lille, Inserm, U908-CPAC-Cell Plasticity and Cancer, F-59000 Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bal-Mahieu
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France. Electronic address: till.bousquet@univ-lille1.fr.
authors.forename: Till
authors.initials: T
authors.lastname: Bousquet
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pellegrini
authors.affiliation: Univ. Yaoundé 1, Laboratoire de Chimie de Coordination, BP 812, Yaoundé, Cameroon.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Ndifon
authors.affiliation: Univ. Lille, Inserm, U908-CPAC-Cell Plasticity and Cancer, F-59000 Lille, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Meignan
authors.affiliation: Univ. Lille, CHU Lille, EA 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Goossens
authors.affiliation: Département de Recherches Médicales, Groupement hospitalier de l'Institut Catholique de Lille, 59000 Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181-UCCS-Unité de Catalyse et Chimie du Solide, F-59000 Lille, France. Electronic address: lydie.pelinski@univ-lille1.fr.
authors.forename: Lydie
authors.initials: L
authors.lastname: Pélinski
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D005296:Ferrous Compounds; D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; C000611509:ferrocenyl indeno(1,2-c)isoquinoline; D004250:DNA Topoisomerases, Type II
keywords: Cytotoxicity; Drug binding; Ferrocene; Indenoisoquinoline; Topoisomerase II inhibitor