Unraveling the crystal structure, stability and drug likeness of 1,3,4-oxadiazole derivatives against Myelofibrosis: a combined experimental and computational investigation

Abstract

Herein, we report the synthesis and characterization of novel 1,3,4-oxadiazole derivatives, 2-methoxybenzyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C1) 2-methoxybenzyl 5-(2-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C2), and methoxybenzyl 5-(3-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C3) obtained through desulfurative cyclization reaction. The compound C2 was crystallized, and its crystal structure was elucidated using single-crystal X-ray diffraction technique. The Hirshfeld surface analysis was carried out to analyze, visualize and globally appreciate the weak interactions involved in crystal packing. These analyses were complemented by Quantum Theory of Atoms In Molecules (QTAIM) and Reduced Density Gradient (RDG), which allowed us to decipher the nature and types of attractive forces that contribute to maintain the crystal structure of the titled compound. Moreover, the ADME profile of the compound was predicted to assess its drug likeness. Finally, in silico studies were performed to explore the binding affinity of the compounds (C1–3) against Myelofibrosis through molecular docking and molecular dynamic simulations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Crystal structure
• 1,3,4-oxadiazole derivatives
• QTAIM
• molecular docking
• molecular dynamics

Acknowledgements

Santhosh C Thank UGC, New Delhi for providing senior research fellowship (DEC 18-100320), Karthik V. thank DST-KSTePS for providing DST fellowship (PHY-05-2022-23/1026). Sadashiva M P grateful to VGST, Government of Karnataka (KSTePS/VGST/K-FIST L1/GRD No. 1038/2021-22/427e). Authors thankful to Dr Tendamudzimu Tshiwawa, Rhodes university for providing high performance computing (CHPC) facility for MD calculations.

Disclosure Statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.