A New Insight into Non-covalent Interactions in 1,4-Disubstituted 1H-1,2,3-Triazole: Synthesis, X-ray structure, DFT calculations, in vitro Lipoxygenase Inhibition (LOX) and in silico Studies

• Published in: Journal of molecular structure 2021-07, Vol.1236, p.130283, Article 130283
• Main Authors: Ahmed, Muhammad Naeem, Shabbir, Sadia, Batool, Bakhtawar, Mahmood, Tariq, Rashid, Umer, Yasin, Khawaja Ansar, Tahir, Muhammad Nawaz, Cassará, M. L. Arias, Gil, Diego M.
• Format: Article
• Language: English
• Subjects: DFT; Docking; LOX; Non-covalent interactions; Triazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130283

•The crystal structure of 1,4-Disubstituted 1H-1,2,3-Triazole derivative has been solved.•A complete analysis of intermolecular interactions were performed.•DFT calculations were used to evaluate the relevance of the main intermolecular contacts.•Lipoxygenase Inhibition (LOX) activity and molecular docking analysis were analyzed. Present work deals with the synthesis, characterization, structural properties and in silico studies of ethyl 6-(4-(cyclohexylmethyl)-1H-1,2,3-triazol-1-yl)pyridine-3-carboxylate (1). The synthesized derivative was characterized by spectroscopic as well as single crystal XRD technique. The structure reveals weak non-covalent contacts such as C-H···π, lone pair···π and π···π stacking interactions along with C-H···O and C-H···N hydrogen bonds to form the supramolecular assembly. A detailed analysis of the intermolecular interactions was performed by using the Hirshfeld surface analysis and energy framework calculations, indicating that the dispersion energy is dominant over the electrostatic one in all the structural dimer studied. In addition, the intermolecular interactions have been characterized using the quantum theory of “atoms in molecules”, molecular electrostatic potential (MEP) and the non-covalent interaction plot (NCI plot) index analysis. Compound displayed the IC50 value of IC50 = 37.40 μM in comparison to reference drug indomethacin (IC50 = 48.25 μM) against lipoxygenase (LOX). Docking studies revealed important interactions and binding energy of the compound in comparison with the standard drugs used. [Display omitted]