Alamri Mohammed A, Alamri Mubarak A
Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia.
Saudi Pharm J. 2021 Oct;29(10):1166-1172. doi: 10.1016/j.jsps.2021.08.016. Epub 2021 Aug 29.
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.
合成了新型基于金刚烷的化合物，并将其作为潜在的σ-2受体配体进行评估。进行了分子对接和50纳秒的分子动力学模拟，以确定这些化合物在σ-2受体活性位点内的结合模式、相互作用机制和稳定性。此外，还探索了药物代谢动力学性质（ADME-T）。还检测了表达σ-2受体的癌细胞系中的细胞毒性。此外，将新化合物的计算机模拟数据和细胞毒性数据与具有高受体结合亲和力和选择性的参考σ-2受体配体进行了比较。数据表明，新化合物与σ-2受体的相互作用方式与参考化合物相当，并且金刚烷可作为骨架来合成具有有用官能团的σ-2受体配体，这些官能团可用于连接用于肿瘤成像或细胞毒性药物递送的部分。
