Weak Noncovalent Interactions in Three Closely Related Adamantane-Linked 1,2,4-Triazole -Mannich Bases: Insights from Energy Frameworks, Hirshfeld Surface Analysis, 11β-HSD1 Molecular Docking and ADMET Prediction.

Structural analysis and docking studies of three adamantane-linked 1,2,4-triazole -Mannich bases (-) are presented. Compounds , and crystallized in the monoclinic 2/, 2 and 2/ space groups, respectively. Crystal packing of was stabilized by intermolecular C-H⋯O interactions, whereas compounds and were stabilized through intermolecular C-H⋯N, C-H⋯S and C-H⋯π interactions. The energy frameworks for crystal structures of - were described. The substituent effect on the intermolecular interactions and their contributions were described on the basis of Hirshfeld surface analyses. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibition potential, pharmacokinetic and toxicity profiles of compounds - were determined using techniques. Molecular docking of the compounds into the 11β-HSD1 active site showed comparable binding affinity scores (-7.50 to -8.92 kcal/mol) to the 11β-HSD1 co-crystallized ligand (-8.48 kcal/mol, 11β-HSD1 IC = 9.9 nM). The compounds interacted with key active site residues, namely Ser170 and Tyr183, via strong hydrogen bond interactions. The predicted pharmacokinetic and toxicity profiles of the compounds were assessed, and were found to exhibit excellent ADMET potential.