Investigation of the crystal structure, supramolecular architecture and in-silico myelofibrosis inhibition of a triazole derivative: a structural and theoretical approach

Abstract

One of the most significant issues in contemporary medicine and pharmacy is the search for efficient, low-toxic anticancer medicines. In this contrast, present work involves the synthesis of 6-(4-bromophenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b[1,3,4]thiadiazine compound and its characterization using various spectroscopic techniques. Structural and Hirshfeld surface analysis inferred that the crystal packing is stabilized by several intra and intermolecular interactions, their nature and strength are corroborated by the quantum theory of atoms in molecules analysis. The H···H and C-H···N strong intra and intermolecular hydrogen bond interactions resulted in the formation of S(5), S(6) self-motifs and R22(10), R66(42) supramolecular ring motifs. Further, the electronic properties of the molecule were obtained using the density functional theory. The charge distribution on the molecular surface are analyzed using the molecular electrostatic potential map and Fukui analysis. The intramolecular hyper conjugations, and charge delocalization in the compound are analyzed by natural bond orbital analysis. The docking studies revealed that the molecule might possess potential anticancer activity against Janus tyrosine kinase 2 protein compared to pacritinib, and in silico ADMET pharmacokinetic properties indicate adherence to Lipinski's rule of five for favorable safety profiles.