Fersiynau electronig

Dogfennau

  • PURE VERSION_2019_CYN_Chem_3105

    Llawysgrif awdur wedi’i dderbyn, 613 KB, dogfen-PDF

    Embargo yn dod i ben: 10/06/21

    Trwydded: CC BY-NC-ND Dangos trwydded

  • CYN_analogue_2019-CHEM_SI

    Llawysgrif awdur wedi’i dderbyn, 649 KB, dogfen-PDF

    Embargo yn dod i ben: 10/06/21

    Trwydded: CC BY-NC-ND Dangos trwydded

Dangosydd eitem ddigidol (DOI)

Cylindrospermopsin (CYN) is an alkaloid biosynthesized by selected cyanobacteria, the cyto- and genotoxic properties of which have been studied extensively by in vitro and in vivo experimental models. Various studies have separately established the role of uracil, guanidine and hydroxyl groups in CYN-induced toxicity. In the present study, we have prepared five synthetic analogues that all possess a uracil group but had variations in the other functionality found in CYN. We compared the in vitro toxicity of these analogues in common carp hepatocytes by assessing oxidative stress markers, DNA fragmentation and apoptosis. All the analogues tested induced generation of reactive oxygen species, lipid peroxidation (LPO) and DNA fragmentation. However, the greatest increase in LPO and increase in caspase-3 activity, an apoptosis marker, was demonstrated by an analogue containing guanidine, hydroxyl and uracil functionalities similar to those found in CYN but lacking the complex tricyclic structure of CYN. We also report a crystal structure of an analogue lacking the hydroxyl group found in CYN which does not show intramolecular H-bonding interactions between the guanidine and the uracil functionalities. The observations made in this work supports the hypothesis that CYN toxicity is a result of an interplay between both of the uracil, hydroxyl and guanidine functional groups.
Iaith wreiddiolSaesneg
Tudalennau (o-i)139-147
Nifer y tudalennau9
CyfnodolynChemosphere
Cyfrol234
Dyddiad ar-lein cynnar10 Meh 2019
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsE-gyhoeddi cyn argraffu - 10 Meh 2019
Gweld graff cysylltiadau