title: 4-(1,2-diarylbut-1-en-1-yl)isobutyranilide derivatives as inhibitors of topoisomerase II.
abstract: The synthesis and biological evaluation of a new library of 4-(1,2-diarylbut-1-en-1-yl)isobutyranilides is described. The new compounds were found to be cytotoxic in the micromolar range in two human tumor cell lines, MCF-7 (mammary gland adenocarcinoma) and HeLa (cervix adenocarcinoma) and two human ovarian cancer cell lines (A2780 and OVCAR5). Detailed studies on the most active compound 6g show that it was able to induce apoptosis and suggest topoisomerase II as a possible intracellular target. The relevance of the interaction of the most active compound with topoisomerase II is demonstrated and supported by docking studies.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy. Electronic address: michalis.christ@gmail.com.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Mikel
authors.initials: M
authors.lastname: Zarate
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Damia
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieraccini
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Dapiaggi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy; CNR-ISTM, Istituto di Scienze e Tecnologie Molecolari, Via Golgi 19, 20133 Milano, Italy; Center for Materials Crystallography, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lo Presti
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
authors.forename: Aída Nelly
authors.initials: AN
authors.lastname: García-Argáez
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy. Electronic address: lisa.dallavia@unipd.it.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
mesh_terms: D000813:Anilides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000813:Anilides; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: McMurry reaction; Tamoxifen derivatives; Topoisomerase I and II