title: Astragalin from Cassia alata induces DNA adducts in vitro and repairable DNA damage in the yeast Saccharomyces cerevisiae.
abstract: Reverse phase-solid phase extraction from Cassia alata leaves (CaRP) was used to obtain a refined extract. Higher than wild-type sensitivity to CaRP was exhibited by 16 haploid Saccharomyces cerevisiae mutants with defects in DNA repair and membrane transport. CaRP had a strong DPPH free radical scavenging activity with an IC(50) value of 2.27 μg mL(-1) and showed no pro-oxidant activity in yeast. CaRP compounds were separated by HPLC and the three major components were shown to bind to DNA in vitro. The major HPLC peak was identified as kampferol-3-O-β-d-glucoside (astragalin), which showed high affinity to DNA as seen by HPLC-UV measurement after using centrifugal ultrafiltration of astragalin-DNA mixtures. Astragalin-DNA interaction was further studied by spectroscopic methods and its interaction with DNA was evaluated using solid-state FTIR. These and computational (in silico) docking studies revealed that astragalin-DNA binding occurs through interaction with G-C base pairs, possibly by intercalation stabilized by H-bond formation.
authors.affiliation: Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus, BA, 45662-900, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Saito
authors.affiliation: Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus, BA, 45662-900, Brazil.
authors.forename: Givaldo
authors.initials: G
authors.lastname: Silva
authors.affiliation: Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus, BA, 45662-900, Brazil.
authors.forename: Regineide Xavier
authors.initials: RX
authors.lastname: Santos
authors.affiliation: Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Grace
authors.initials: G
authors.lastname: Gosmann
authors.affiliation: Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus, BA, 45662-900, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pungartnik
authors.affiliation: Laboratório de Biologia de Fungos, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus, BA, 45662-900, Brazil.
authors.forename: Martin
authors.initials: M
authors.lastname: Brendel
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002366:Cassia / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006238:Haploidy; D020128:Inhibitory Concentration 50; D044949:Kaempferols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D018515:Plant Leaves / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D014732:Vibration
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; D044949:Kaempferols; C006552:kaempferol; C001579:astragalin