Author:
Al-Wahaibi Lamya H.,Joubert Jacques,Blacque Olivier,Al-Shaalan Nora H.,El-Emam Ali A.
Abstract
Abstract5-(Adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole (4) was identified as a potential 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor and this paper describes the in-depth structural analysis thereof. Compound 4 was synthesized in a 92% yield and its 3D-structure confirmed by single-crystal X-ray diffraction. Hirshfeld surface analysis indicated that H…H, C-H…C, C-H…Cl and especially C-H…N hydrogen bond interactions are the primary contributors to the intermolecular stabilisation in the crystal. In order to explore the properties of 4, free from the influence of the crystal field, density functional theory (DFT) calculations were conducted. Results indicated that the DFT optimized geometry of 4 produced a conformer (4a) that is significantly different from the crystal structure. Further experiments confirmed that the crystal structure is not the absolute minimum conformation. This indicated that the crystal packing forces has significantly influenced the conformation thereof. Frontier molecular orbital energies and net atomic charges were also calculated to elucidate the electronic properties of 4a. These results provided insight into areas of the molecule that may present with the ability to form binding interactions at the 11β-HSD1 active site. Molecular docking experiments revealed important intermolecular interactions between 4a and 11β-HSD1. These results indicate that 4 may be considered for further drug design endeavors.
Funder
Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Research Group Program
Publisher
Springer Science and Business Media LLC
Cited by
49 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. A methodical investigation on the growth and characterization of a third-order nonlinear optical novel co-crystal of 8-hydroxyquinolinium phthalate: X-ray, Hirshfeld surface, optical, mechanical, thermal and DFT analysis;Materials Research Bulletin;2024-01
2. Rationally designed C-3 sulfenylated 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one based fluorescent probe for recognition of Fe3+;Journal of Molecular Structure;2023-12
3. Investigation of antituberculosis, antimicrobial, anti-inflammatory efficacies of newly synthesized transition metal(II) complexes of hydrazone ligands: structural elucidation and theoretical studies;Scientific Reports;2023-09-23
4. An oxalato-bridged dimetallic heptanuclear [K5IFe2III] complex anion with guanidinium as counter cation: Synthesis, crystal structure, Hirshfeld surface analysis and magnetism;Polyhedron;2023-09
5. Precisely designed oxazolonaphthoimidazo[1,2-a]pyridine-based sensor for the detection of Fe3+ and DCP with cell imaging application;Journal of Photochemistry and Photobiology A: Chemistry;2023-09