Effective Antitumor Candidates Based upon Ferrocenylseleno-Dopamine Derivatives: Growth Inhibition by Induction Cell Apoptosis and Antivascular Effects

Abstract

One ferrocenyl-dopamine (L1) and four ferrocenylseleno-dopamine derivatives (L2−L5) were designed and prepared with different structural parameters, such as chalcogen atoms, cycle, and semirigidity. The best in vitro anticancer activity occurred with 1,5-diselena[8]ferrocenophane L5, which inhibited cancer cell growth at the lowest micromolar concentrations. The biological studies showed that L5 arrested the cell cycle in G1 phase and induced apoptosis by activating caspase 3/9, also inhibiting endothelial cell (HUVECs) formation. It exhibited better in vivo antitumor activity in mice bearing HepG2 tumor xenograft in comparison to free dopamine. The results suggest that the excellent biological activities can be attributed to the synergetic effect of the ferrocenophane, chalcogen atom, and catechol group.

Planar Chiral Ferrocene Cyclopalladated Derivatives Induce Caspase-Dependent Apoptosis and Antimetastasis in Cancer Cells

“…However, the IC 50 value of compounds 3 and 7 were more potent than compounds 15 and 19 , though the IC 50 value of compound 11 was less potent than compound 23 . These results suggest the half-wave may have an impact on the cytotoxicity of those cyclopalladated candidates, but it was not a major factor …”

“…The cyclic voltammograms (CVs) were recorded as a reported method . In brief, the methanol/acetonitrile (v/v 1/1) solution was used as the electrolyte with 0.1 M [NBu 4 ]­[PF 6 ] as the supporting electrolyte.…”

Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy

“…The six new derivatives, F1c, F1d, F2b, F3b, F4a and F4b, were synthesized following the reported methods as shown in Scheme S1, † 12 and the detailed synthetic processes and related characterization data are provided in the ESI. † Spectroscopic studies were carried out and confirmed the structure of the as-prepared compounds (Fig.…”

“…[5][6][7][8][9][10] Up to now, the ferrocifen family developed mainly by Jaouen's group is one of the real breakthroughs in modern medicinal organometallic chemistry as anticancer drug candidates. [5][6][7]9 Inspired by the promising biological activity of ferrocenyl selenoethers, [11][12][13] our group has previously reported a series of ferrocenylseleno-dopamine derivatives with dopamine units on the backbone, F1a, F1b, F2a and F3a listed in Table 1. These compounds were found to induce carcinoma cell apoptosis and inhibit angiogenesis of vessels in hepatocellular carcinoma.…”

“…These compounds were found to induce carcinoma cell apoptosis and inhibit angiogenesis of vessels in hepatocellular carcinoma. 12 It was found that the chain property between the ferrocene part and the catechol group played an important role in the anticancer properties, for example, the semi-rigidity and the rich π-electron of the benzene ring in F1b display a potent performance of anticancer activity. With the target to optimize antitumor efficacy, in the current study, six new derivatives listed in Table 1 were designed to fine-tune structural parameters such as spacer chain length (F1c, F1d), semi-rigidity (F2b), tertiary amine (F3b and F4b), or more ferrocene units (F4a and F4b).…”