Synthesis, characterization and evaluation of novel ferrocenylmethylamine derivatives as cytotoxic agents

Abstract

The present report describes a new series of amide functionalized 2 0-and 3 0-aminomethylferrocene derived from ferrocenylmethylamine. The compounds 1a-5a and 1b-5b were characterized by microanalysis, 1 H, 13 C NMR, UV-visible, fluorescence, FTIR, thermogravimetric and crystallographic techniques. The X-ray analysis demonstrated the ability of these molecules to form various intermolecular hydrogen bonding interactions, as verified by Hirshfeld surface analysis. All the compounds were evaluated against MCF 7, IMR 32, HepG2 and immortal L132 cell lines by MTT assay and the results were compared with cisplatin. Interestingly, many compounds were very active against all the investigated cell lines and proved to be more potent as cytotoxic agents than cisplatin. The western blot, gene expression, mitochondrial membrane potential and flow cytometry study were used to investigate the mode of action of these derivatives as antitumor agents. The results showed apoptotic property of the compounds by modulating inflammatory pathway against human tumor cells of different origin. We performed the density functional theory calculations and molecular docking to rationalize the experimental results. K E Y W O R D S amide functionalized 2 0-and 3 0-aminomethylferrocene, anticancer, apoptosis, molecular docking, X-ray diffraction

N‐Allyl‐N‐ferrocenylmethylamines andansa‐Ferrocenylmethylamines: Synthesis, Structure, and Biological Evaluation

“…Similarly, strongly cytotoxic ferrocenyl amino phosphines with IC 50 =6.9 μg mL −1 against HT1376 cells, or IC 50 <5 μg mL −1 against Hep3B cells, have been reported [7g,27] . In previous studies, [7e,i] simple ferrocenyl amines with activities in vitro against tumour cells comparable to those presented in Table 1 have been displayed. In some other contributions, however, ferrocenyl amines have been described as inactive or having very little antitumour activity [7a,28,29] .…”

In‐depth study of the heme‐binding ability to five heavy metals: Hg, Cd, Pb, Cr, and As

“…Density functional theory (DFT) is often used in the simulation and prediction of metal complexes, and studies have shown that results of DFT calculations are highly consistent with experimental results. [26][27][28][29][30] Indeed, theoretical DFT calculations may be suitable replacements for conventional experimental research. [31][32][33] Although DFT has been used to analyze heme and heme derivatives.…”