Insights into the crystal structure of two newly synthesized quinoxalines derivatives as potent inhibitor for c-Jun N-terminal kinases

Abstract

Two new compounds namely, ethyl (2E)-3-(dimethylamino)-2-(3-methoxyquinoxalin-2-yl)propen-2-enoate (II) and ethyl 2-(3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydroquinoxalin-2-yl)-3-phenylpropanoate (III) have been synthesized from ethyl 2-(oxo-3,4-dihydroquinoxalin-2-yl) acetate (I). The compounds were characterized using NMR (¹H and ¹³C), Fourier transform infrared and confirmed by single crystal X-ray diffraction studies. The quinoxaline portion of II is almost planar with the substituent containing the dimethylamino and carboxyethyl groups rotated well out of its mean plane. In the crystal, C—H···O and C—H···N hydrogen bonds as well as C—H···π(ring) interactions form chains having a U-shaped cross-section and running along the c-axis direction. Two sets of pair-wise C—H···O hydrogen bonds connect the chains into corrugated sheets. In III, the three substituents on the dihydroquinoxaline moiety are rotated well out of its mean plane. Three sets of C—H···O hydrogen bonds as well as C—H···π(ring) and π–π-stacking interactions form layers approximately parallel to [001]. These are associated along the c-axis direction by additional C—H···π(ring) interactions. Additionally, the Hirshfeld surface analyses showed that the H···H contact is the most important interaction for both II and III. In addition to this, molecular docking and dynamics studies were carried for these two compounds with the c-Jun N-terminal kinases (JNK1) molecule.

Communicated by Ramaswamy H. Sarma

Keywords:

• Quinoxaline
• crystal structure
• Hirshfeld surface analysis
• molecular docking
• molecular dynamics

Acknowledgements

The support of Tulane University for the Tulane Crystallography Laboratory is gratefully acknowledged. The publication was also prepared with the support of the ‘RUDN University Program 5-100’. We also thank the National Center for High-performance Computing (Taiwan) for providing computing time. Special thanks are also due to the reviewers and the editor for their helpful suggestions and comments.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors gratefully acknowledge Mohammed V University (Morocco) for the financial assistance and facilitation to facilitate this study.