Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches

Abstract

Neuroblastoma can be accessed with compounds of larger sizes and wider polarities, which do not usually cross the blood–brain barrier. Clinical data indicate cases of spontaneous regression of neuroblastoma, suggesting a reversible point in the course of cell brain tumorigenesis. Dual specificity tyrosine-phosphorylation-regulated kinase2 (DYRK2) is a major molecular target in tumorigenesis, while curcumin was revealed to be a strong inhibitor of DYRK2 (PBD ID: 5ZTN). Methods: in silico studies by CLC Drug Discovery Workbench (CLC) and Molegro Virtual Docker (MVD) Software on 20 vegetal compounds from the human diet tested on 5ZTN against the native ligand curcumin, in comparison with anemonin. In vitro studies were conducted on two ethanolic extracts from Anemone nemorosa tested on normal and tumor human brain cell lines NHA and U87, compared with four phenolic acids (caffeic, ferulic, gentisic, and para-aminobenzoic/PABA). Conclusions: in silico studies revealed five dietary compounds (verbascoside, lariciresinol, pinoresinol, medioresinol, matairesinol) acting as stronger inhibitors of 5ZTN compared to the native ligand curcumin. In vitro studies indicated that caffeic acid has certain anti-proliferative effects on U87 and small benefits on NHA viability. A. nemorosa extracts indicated potential benefits on NHA viability, and likely dangerous effects on U87.

Anti-Proliferative Potential of Cynaroside and Orientin—In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies

“…By MVD simulation (Table 2), the efficacy of 7-Lut (score −128.51) and 8-Lut (score −126.66) in interfering with DYRK2 activity was confirmed; both compounds positioned as stronger inhibitors of 5ZTN in comparison with the native ligand curcumin (score −115.85). Former studies on DYRK2 and 5ZTN [24] indicated luteolin aglycone scores of −71.01 by CLC simulation and −104.91 by MVD simulation; therefore, luteolin aglycone is a weaker 5ZTN inhibitor than curcumin and the two luteolin glycosides as well. Tables 1 and 2 present comparative data on the intermolecular interactions, explicitly hydrogen bonding (HB) between the native ligand curcumin docked in complex with the DYRK2 binding site, in comparison with the two test ligands, 7-Lut and 8-Lut.…”

“…By MVD simulation (Table 2), the efficacy of 7-Lut (score −128.51) and 8-Lut (score −126.66) in interfering with DYRK2 activity was confirmed; both compounds positioned as stronger inhibitors of 5ZTN in comparison with the native ligand curcumin (score −115.85). Former studies on DYRK2 and 5ZTN [24] indicated luteolin aglycone scores of −71.01 by CLC simulation and −104.91 by MVD simulation; therefore, luteolin aglycone is a weaker 5ZTN inhibitor than curcumin and the two luteolin glycosides as well. * Ligands' structures were retrieved from the PubChem database [25] and submitted to minimization using Molecular Mechanics Force Field (MMFF) [26] using Spartan v. 14 software (Wavefunction, Inc., Irvine, CA, USA); atoms' labeling was randomly chosen by the software.…”

“…By MVD simulation (Table 2), the efficacy of 7-Lut (score −128.51) and 8-Lut (score −126.66) in interfering with DYRK2 activity was confirmed; both compounds positioned as stronger inhibitors of 5ZTN in comparison with the native ligand curcumin (score −115.85). Former studies on DYRK2 and 5ZTN [24] Tables 1 and 2 present comparative data on the intermolecular interactions, explicitly hydrogen bonding (HB) between the native ligand curcumin docked in complex with the DYRK2 binding site, in comparison with the two test ligands, 7-Lut and 8-Lut. The docking simulations were performed by CLC Drug Discovery Workbench Software (QIAGEN, Aarhus, Denmark) and MVD Molegro Virtual Docker Software (QIAGEN, Aarhus, Denmark).…”