Abstract
Novel adamantane-based compounds were synthesized and assessed as potential sigma-2 receptor ligands. Molecular docking and 50 ns molecular dynamic simulation were carried out to determine the binding modes, mechanism of interaction, and stability of these compounds within the active site of the sigma-2 receptor. In addition, the ADME-T properties have been explored. The cytotoxicity in cancer cell lines that express sigma-2 receptors was also examined. In addition, the in silico and cytotoxicity data for the new compounds were compared to a reference sigma-2 receptor ligand with high receptor-binding affinity and selectivity. The data suggests that the new compounds interact with the sigma-2 receptor in a comparable manner to the reference compound, and that adamantane can be used as a scaffold to synthesize sigma-2 receptor ligands with useful functional groups that can be used to conjugate moieties for tumor-imaging or cytotoxic cargo delivery. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).