Design, synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor.

PURPOSE: Vortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2. METHODS: In this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper. RESULTS: Based on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine. CONCLUSION: This study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.

Design, synthesis and biological evaluation of vortioxetine derivatives as new COX-1/2 inhibitors in human monocytes.

In order to identify a suitable alternative to non-steroidal anti-inflammatory drugs (NSAIDs) we aimed to develop derivatives of vortioxetine, a multimodal anti-depressive drug that has been shownpreviously to be endowed withanti-inflammatory activity in human monocytes/macrophages. Vortioxetine (1) was synthesized in good yield and different alkyl and aryl derivatives were prepared based on their structural diversity and easy availability. The compounds were tested on human monocytes isolated from healthy donors for theireffect on superoxide anion production and cytokine gene expression, and for COX-1/2 gene expression and activity modulation. Moreover, a docking study was performed to predict the interactions between the synthesized compounds and COX-1 and COX-2. Correlating experimental biological data to the molecular modelling studies, it emerged that among the novel compounds, 6 was endowed of antioxidant and anti-COX-1 activity, vortioxetine and 3 were good antioxidants and mild anti-COX-1/2 inhibitors, while 7 was a good anti-COX-1/2 inhibitor and 11 was more specific versus COX-2.