title: Role of 13-(di)phenylalkyl berberine derivatives in the modulation of the activity of human topoisomerase IB.
abstract: Topoisomerases IB are anticancer and antimicrobial targets whose inhibition by several natural and non-natural compounds has been documented. The inhibition effect by berberine and some 13-(di)phenylalkyl berberine derivatives has been tested towards human topoisomerase IB. Derivatives belonging to the 13-diphenylalkyl series display an efficient inhibition of the DNA relaxation and cleavage step, that increases upon pre-incubation with the enzyme. The religation step of the enzyme catalytic cycle is not affected by compounds and only slightly upon pre-incubation. The binding of the protein to the DNA substrate occurs also in the presence of the compounds, as monitored by a DNA shift assay, indicating that the compounds are not able to inhibit the formation of the enzyme-DNA complex but that they act as catalytic inhibitors.
authors.affiliation: University of Rome Tor Vergata, Department of Biology, Via Della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Vieira
authors.affiliation: University of Rome Tor Vergata, Department of Biology, Via Della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castelli
authors.affiliation: University of Rome Tor Vergata, Department of Biology, Via Della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Falconi
authors.affiliation: University of Rome Tor Vergata, Department of Biology, Via Della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Takarada
authors.affiliation: Naxospharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Fiorillo
authors.affiliation: Naxospharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Buzzetti
authors.affiliation: Naxospharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lombardi
authors.affiliation: University of Rome Tor Vergata, Department of Biology, Via Della Ricerca Scientifica, 00133 Rome, Italy. Electronic address: desideri@uniroma2.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
mesh_terms: D001483:Base Sequence; D001599:Berberine / Q000737:chemistry* / Q000494:pharmacology*; D055162:Biocatalysis / Q000187:drug effects; D002713:Chlorine / Q000737:chemistry; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship
chemical_list: D001599:Berberine; D002713:Chlorine; D004247:DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: Berberine chloride; Human topoisomerase IB; Natural compound