NFBTA: A Potent Cytotoxic Agent against Glioblastoma

Abstract

Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.

Bioactivity and Molecular Docking Studies of Derivatives from Cinnamic and Benzoic Acids

“…In consequence, the docking predicted complexes are not necessarily stable. Previous studies have shown that many predicted ligandreceptor complexes, although presenting favorable interactions might not be feasible [44,45]. To further refine the possible mechanism of action of compound 7, MD simulations and MM-PBSA calculations were performed as described in the Materials and Methods section.…”

“…The OMEGA software [41] was used to obtain the initial 3D structure of compound 7, and AM1-BCC charges were added to it with MOLCHARGE [42]. Molecular docking of compound 7 to its potential targets was performed with Gold [43] following the same procedure as in our previous research [44,45]. Water molecules, cocrystalized ligands, and cofactors not involved in ligand binding were removed from the receptors.…”

Alkyl and Aryl Derivatives Based on p-Coumaric Acid Modification and Inhibitory Action against Leishmania braziliensis and Plasmodium falciparum

“…Overall, the docking results did not allow for confident selection of the most probable compound 9 targets. Post-processing of predicted docking complexes using Molecular Dynamics (MD) simulations along with estimations of free energies of binding can help refine target prioritization [ 44 , 65 ]. Calculations were thus performed (described in the Methods section) to estimate the free energies of binding for compound 9 to its predicted targets using the MD simulations data.…”

“…Molecular docking followed the same protocol described in our previous publications [ 44 , 65 ]. The initial three-dimensional conformation of compound 9 was obtained with OpenEye Omega [ 79 ]; and AM1-BCC partial atomic charges were added to it using Molcharge [ 80 ].…”

Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 Mpro Protease

“…The selection of the most probable binding modes of each compound to M pro was carried out following the previously described consensus scoring methodology [55,57,58]. Consensus scoring took place independently for each compound to rank its 30 predicted binding modes.…”