Natural products are sources of secondary metabolites with wide pharmacological
applicability, including anticancer. Biflorin, a prenylated ortho-naphthoquinone that has
been isolated from the roots of the Capraria biflora L. plant, has stood out as a potent
prototype antitumor drug. However, despite promising potential, its antineoplastic
capacity is incipiently applied to gastric cancer, one of the most incidente, aggressive
and lethal cancers, nationally and globally. In this context, this study aimed to analyze
the structure-toxicity relationship of biflorin by the redox in silico mechanism, as well
as the in vitro cytotoxic and anti-invasive potential, using as a model strains of
intestinal-type gastric adenocarcinoma metastatic (AGP01) and isolated from primary
tumor (ACP03). In silico analysis showed that biflorin has a differentiated reactivity
characteristic and can act as electron donor or acceptor in nucleophilic and
electrophilic reactions, respectively. Moreover, when compared to other natural
naphthoquinones such as β-lapachone and lapachol, it presented better redox
properties and reactivity conditions, but with less toxic effect due to their ability to form
more stable intermediates. The molecular simplification of biflorin also allowed to infer
that the ortho-naphthoquinone functional group is probably the most related to
naphthoquinones toxicity. Additionally, biflorin showed cytotoxic activity at
considerably low concentrations for both strains, however, cytotoxicity was more
pronounced for AGP01 (IC50 3.1 μM) compared to ACP03 (IC50 4.5 μM) at 48h
treatment. Regarding antimetastatic activity, biflorin reduced the cell invasion capacity
of the AGP01 strain only (p <0.0001). The results indicate that biflorin has cytotoxic
activity for both gastric cancer strains AGP01 and ACP03, as well as anti-invasive
specifically for metastatic cells AGP01. In addition, it was possible to clarify the
probable selective cytotoxicity of biflorin based on its structural reactivity.
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