Synthesis, Characterization, and In Silico Evaluation of Pyrazole- 1,3,4-Oxadiazole Scaffolds as Aurora Kinase Inhibitors

Abstract

A robust and efficient synthetic strategy for a series of new pyrazole-linked 1,3,4-oxadiazole
scaffolds was synthesized and structurally characterized 1H-NMR, 13C NMR, IR and ESI-MS.
Comprehensive insilico studies were conducted to assess the inhibitory potential of all synthesized
molecules towards aurora kinase, a critical regulator of cell cycle progression. Molecular docking of the
synthesized derivatives revealed that molecules 4g and 4h exhibited superior Glide scores, glide energy,
human oral absorption, comparable to clinically relevant aurora kinase inhibitor danusertib. Markedly,
the conserved interaction with the key active site residues was consistently observed across the most
active molecules and danusertib, underscoring its pivotal role in aurora kinase inhibition. Collectively,
these findings highlight molecules 4g and 4h as promising lead molecules for further development as
potent aurora kinase inhibitors with potential anti-cancer applications.