Theoretical Study of the Stability and Chemical Reactivity of a Series of Dihydropyrazoles with Antiproliferative Activities

In recent years, the number of cancer cases are increasing particularly that of prostate. In this work, we were interested in anticipating dihydropyrazole-cancer cell interactions and their anti-prostatic activity by studying the chemical reactivity and stability of a series of six dihydropyrazole compounds. This study was carried out on six molecules from a series of antiproliferative dihydropyrazoles (DP) substituted by halogens and cyclic molecules, using density functional theory at the B3LYP/6-31+G (d,p) level. Obtained at 298 K thermodynamic formation parameters confirm the formation and existence of the series of studied molecules. Boundary molecular orbitals examination, including the energy gap (ΔE), electronegativity (χ), chemical hardness (η) and electrophilicity index (ω), provided a deeper perspective on molecular properties. As a result, among studied compounds, DP-1 and DP-5 stand out for having the highest energy gaps between boundary orbitals, making them more stable and less reactive. In addition, DP-1 was found to be the best electron donor and the hardest compound among examined ones. Analysis of local descriptors, isodensity and electrostatic potential maps identified the two nitrogen atoms as the preferred sites for electrophilic and nucleophilic attack. However, the two nitrogen atoms contained in the pyrazole ring of dihydropyrazoles (DP) with one in sp3 and the other sp2 hybridization state are the preferred sites for electrophilic and nucleophilic attacks, respectively.