In silico development of new PET radiopharmaceuticals from mTOR inhibitors.

Rapamycin (or sirolimus) is a macrolide that has shown to be useful as an immunosuppressant and that was studied in metabolic, neurological, or genetic disorders. Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. This work aimed to evaluate the utility of several compounds obtained from rapamycin and its semi-synthetic analogs everolimus and temsirolimus as possible radiopharmaceuticals oriented to this protein. Density Functional Theory calculations of these molecules were made and further analysis of the dual descriptor, charges populations, and of the electrostatic potential surfaces were performed. Molecular docking simulations were used to evaluate the interactions of the rapamycin with the studied candidates. They allowed us to propose two strategies for the synthesis of novel compounds based on electrophilic reactions. Molecular docking results also helped us to eliminate molecules that did not interact correctly with the target. Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed 18F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system.

Endocrine vigilance in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for a pandemic that emerged in December 2019. Heterogeneous clinical forms are described from asymptomatic to severe hypoxaemic acute respiratory syndrome with multisystem organ failure. The impact of this coronavirus disease 2019 on the endocrine glands remains unknown. However, the results of previous studies on viruses from the same family allow us to write proposals for patients followed for chronic endocrine diseases. Currently, if these subjects are infected with SARS-CoV-2, they must not stop their treatment. In some cases, hormone replacement doses have to be increased. In case of worsening clinical signs, hormonal biological monitoring must be done. This article will be helpful for improving the management of chronic endocrine diseases that could affect thyroid, adrenals, gonads and pituitary gland functions. Proposals could be applied in COVID-19 infected subjects or in those who have been in contact with COVID-19 infected people.