Structural studies, DFT computational analysis and inhibitory potential of (E)-N'-(2-bromophenyl)-N-(2,6-diisopropylphenyl)formamidine against CDK1 and CDK2

• (E)-N'-(2-bromophenyl)-N-(2,6-diisopropylphenyl)formamidine (BDF) was successfully synthesized and characterized. • The X-ray crystal structure of BDF was reported. • BDF showed promising inhibitory potential against CDK1 and CDK2. • Chemical reactivity and stability of BDF was investigated by exploring DFT studies. • Hirshfeld surface analysis of BDF was studied. Compound ( E )- N' -(2-bromophenyl)- N -(2,6-diisopropylphenyl)formamidine ( BDF ) was synthesized and elucidated by FT-IR, UV–Visible, 13 C & 1 H -NMR, spectroscopy as well as mass spectrometry techniques. The crystal structure of BDF was affirmed using single crystal X-ray diffraction technique. The molecular conformation of BDF is such that the dihedral angle between its phenyl rings is 57.62(10)° while the two rings were orientated with the formamidine functional group in a synclinical form. The intermolecular N—H…N together with C—H…π hydrogen bonding patterns exist in the crystal packing of BDF and Hirshfeld surface (HS) analysis was carried out to study their significance in the formation of one-dimensional supramolecular architectures within the crystal lattice of BDF . The geometry parameters of BDF were investigated using various basis sets and the B3LYP/6–311++ G (d,p)cc-PVTZ-PP level of theory gave the closest match to the experimental values. The calculated E LUMO , E HOMO and energy band gap (∆E) values for BDF are -0.85 eV, -5.97 eV, and 5.12 eV respectively. The inhibitory potential of BDF against cyclin-dependent kinase 1 (CDK1) and 2 (CDK2) were investigated through molecular docking, molecular dynamics (MD) simulations as well as post-MD which include Root Mean Square Fluctuation (RMSF), Root of Gyration (RoG) and Root Mean Square Deviation (RMSD). The molecular docking studies revealed that BDF has better docking scores than known inhibitor (roscovitine) of CDK1 and CDK2. Outcomes of the MD simulation unveiled that BDF exhibited good free binding energies against the two proteins but did not outshine the ones for roscovitine. However, further optimization of BDF could enhance its binding energies against CDK1 and CDK2. Pharmacokinetics and pharmacological approximation revealed that BDF did not violate the Lipinski’ rule and this indicates its tendency to be orally bioavailable and to a lesser extent toxic.