Abstract:
BACKGROUND: 2-Methoxyestradiol is known to have antitumour and antiproliferative action in vitro and in vivo.
However, when 2-methoxyestradiol is orally administered, it is rapidly oxidized by the enzyme 17β-hydroxysteriod
dehydrogenase in the gastrointestinal tract. Therefore, 2-methoxyestradiol never reaches high enough concentrations
in the tissue to be able to exert these antitumour properties. This resulted in the in silico-design of 2-methoxyestradiol
analogues in collaboration with the Bioinformatics and Computational Biology Unit (UP) and subsequent synthesis by
iThemba Pharmaceuticals (Pty) Ltd (Modderfontein, Midrand, South Africa). One such a novelty-designed analogue is
2-ethyl-3-O-sulphamoyl-estra-1, 3, 5(10)16-tetraene (ESE-16).
METHODS: This pilot study aimed to determine the morphological effect and possible generation of reactive
oxygen species by ESE-16 on erythrocytes and platelet samples (with and without added thrombin) by means
of scanning electron microscopy, transmission electron microscopy and flow cytometry.
RESULTS: Erythrocytes and platelets were exposed to ESE-16 at a concentration of 180nM for 24 hours. Scanning- and
transmission electron microscopy indicated that ESE-16 did not cause changes to erythrocytes, platelets or fibrin networks.
Flow cytometry measurements of hydrogen peroxide and superoxide indicated that ESE-16 does not cause an increase in
the generation of reactive oxygen species in these blood samples.
CONCLUSION: Further in vivo research is warranted to determine whether this novel in silico-designed analogue may impact
on development of future chemotherapeutic agents and whether it could be considered as an antitumour agent.
