A Structural and In Silico Investigation of Potential CDC7 Kinase Enzyme Inhibitors

A crucial role in the regulation of DNA replication is played by the highly conserved CDC kinase. The CDC7 kinase could serve as a target for therapeutic intervention in cancer. The primary heterocyclic substance is pyrazole, and its derivatives offer great potential as treatments for cancer cell lines. Here, we synthesized the two pyrazole derivatives: 4-(2-(4-chlorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-1) and 4-(2-(2,4-difluorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-2). The structural confirmation of both the compounds at the three-dimensional level is characterized using single crystal X-ray diffraction and density functional theory. Furthermore, the in silico chemical biological properties were derived using molecular docking and molecular dynamics (MD) simulations. PYRA-1 and PYRA-2 crystallize in the P-1 (a = 8.184(9), b = 14.251(13), c = 15.601(15), α = 91.57(8), β = 97.48(9), 92.67(9), V = 1801.1(3) 3, and Z = 2) and P21/n (a = 14.8648(8), b = 8.5998(4), c = 15.5586(8), β = 116.47(7), V = 1780.4(19) 3, and Z = 4), space groups, respectively. In both PYRA-1 and PYRA-2 compounds, C–H···O intermolecular connections are common to stabilize the crystal structure. In addition, short intermolecular interactions stabilizes with C–H···π and π–π stacking. Crystal packing analysis was quantified using Hirshfeld surface analysis resulting in C···H, O···H, and H···H contacts in PYRA-1 exhibiting more contribution than in PYRA-2. The conformational stabilities of the molecules are same in the gas and liquid phases (water and DMSO). The docking scores measured for PYRA-1 and PYRA-2 with CDC7 kinase complexes are −5.421 and −5.884 kcal/mol, respectively. The MD simulations show that PYRA-2 is a more potential inhibitor than PYRA-1 against CDC7 kinase.