title: Pyrroloquinolinone-based dual topoisomerase I/II inhibitor.
abstract: A new series of pyrroloquinolinones bearing different alkylamino side chains were synthesized and evaluated as cytotoxic compounds against three different human tumor cell lines (HeLa, HL-60 and A431). Some compounds showed interesting antiproliferative activity, in particular against A431 cells. The compounds were tested for their ability to counteract topoisomerase II relaxation activity and the most interesting one (3c) was tested also against topoisomerase I, resulting a dual inhibitor. The molecular interactions between 3c and the intracellular targets were finally investigated through molecular modeling simulations.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marzaro
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferrarese
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Gia
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy. Electronic address: adriana.chilin@unipd.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Chilin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D015363:Quinolones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: Dual activity; Molecular docking; Pyrroloquinolinone; Topoisomerase