0000000000222762
AUTHOR
Concetta Imperatore
Marine inspired antiplasmodial thiazinoquinones: synthesis, computational studies and electrochemical assays
In the search for new antimalarials, we used the quinone scaffold of marine secondary metabolites as a chemical starting point to synthesize new thiazinoquinone compounds. Most of synthetic derivatives have shown a significant pharmacological activity and some structural requirements, critical for both the antiplasmodial effect and cytotoxicity, have been evidenced. The redox properties of the prepared compounds have been investigated by computational studies and electrochemical assays, which indicated that a higher antiplasmodial activity of some thiazinoquinones is related to their greater ability to form the semiquinone species and strongly interact with free Fe(III)-protoporphyrin IX.
Insight into the Mechanism of Action of Marine Cytotoxic Thiazinoquinones
The electrochemical response of four natural cytotoxic thiazinoquinones isolated from the Aplidium species was studied using conventional solution-phase and solid-state techniques, based on the voltammetry of immobilized particles methodology. The interaction with O-2 and electrochemically generated reactive oxygen species (ROS) was electrochemically monitored. At the same time, a molecular modeling study including density functional theory (DFT) calculations was performed in order to analyze the conformational and electronic properties of the natural thiazinoquinones, as well as those of their reduced intermediates. The obtained electrochemical and computational results were analyzed and c…