Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety

Abstract

Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested.For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV-Vis, 1 H and 13 C NMR spectroscopy and X-ray crystallography. Regarding their structureactivity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of dimers and chains formed by the N-H•••O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV-Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation.

Exploration of DFT and TD-DFT computation to investigate the interaction between paracetamol and lithium or its compounds

“…It provides the energy of different frontier molecular orbital, optimization energy, free energy and others for the chemical entities. Here, the authors have applied RB-B3LYP method with the basis set 6-311G(D,P) using Gaussian software [25] , [26] , [27] . Different thermodynamic parameters have been calculated at 298 K and 310 K in default and water.…”

An insight of novel eutectic mixture between thiazolidine‐2,4‐dione and zinc chloride: Temperature‐dependent density functional theory approach

“…DFT calculation can be used to determine heat of formation, charge mobility, interaction energy, electronic energy, polarizability, zero‐point energy, entropy, and Gibb's free energy. [ 18–25 ] Viscosity of eutectic mixtures is a key limiting factor in their use. The viscosity of eutectic mixtures is pretty high, being 100–1000 times that of water or typical organic solvents because of hydrogen bond in eutectic mixtures.…”