Crystal structure of 1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3,5-diphenyl-1H-pyrazole and molecular docking studies of 1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3,5-diphenyl-1H-pyrazole and 5-methyl-1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3-phenyl-1H-pyrazole towards tyrosine kinases

• Published in: Journal of molecular structure 2021-08, Vol.1237, p.130345, Article 130345
• Main Authors: Abu-Safieh, Kayed, El-Barghouthi, Musa I., Khanfar, Monther A., Salameh, Bader A., Al-Aqrabawi, Islam S., Hourani, Baker Jawabrah Al, Ali, Basem F.
• Format: Article
• Language: English
• Subjects: Bipyrazole; Crystal structure; Hydrogen bonding; Molecular docking; Pyrazole; Supramolecular structure
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130345

•Crystal structure and molecular structure of 1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3,5-diphenyl-1H-pyrazole.•3D framework structure.•C–H···O and C–H···N interactions and crystal packing.•Molecular docking studies towards tyrosine kinases.•Strong interactions between substituted pyrazole ring and the studied proteins. The title compound, C20H17N5O2, crystallizes with three independent molecules (A, B and C) in the asymmetric unit with almost identical geometrical parameters. The molecules are far from planar as a result of steric repulsion between the rings. In the crystal, the A, B and C molecules are linked by a pair of C—H···O and one C—H···N hydrogen bonds forming A, B and C trimer. These trimers are further linked by a fourth C—H···N hydrogen bond, forming layers that stack along 101¯ plane which are in turn linked by fifth C—H···O interactions, along b-axis. Interlayers π···π interactions between different pyrazole rings of two molecules add extra lattice supramolecularity. All interactions form a compact 3D supramolecular structure. Molecular docking techniques are carried out to explore the interactions of the title compound and closely related structures with bcr/abl and epidermal growth factor receptor tyrosine kinases (EGFR and HER2) to interpret the cytotoxic activities of some of them toward K562 and MCF-7 cancer cell lines. Results of the molecular docking reveal strong interactions between the title compound and one of the closely related structure (muting the phenyl group to methyl at position 5 in pyrazole ring) with the studied proteins. Structure of 1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3,5-diphenyl-1H-pyrazole and molecular docking studies of 1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3,5-diphenyl-1H-pyrazole and 5-methyl-1-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)-3-phenyl-1H-pyrazole towards tyrosine kinases are reported. [Display omitted]