Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action

Skoupilová, Hana; Bartošík, Martin; Sommerová, Lucia; Pinkas, Jiřı́; Vaculovič, Tomáš; Kanický, Viktor; Karban, Jindřich; Hrstka, Roman

doi:10.1016/j.ejphar.2019.172825

Cited by 33 publications

(14 citation statements)

References 32 publications

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“…Meanwhile, iron, the most abundant transition metal in the human body, after some early challenges in the search for an organometallic approach compatible with biology [ 9 ], is now gradually working its way towards the top priorities. This effectively first became clear once ferrocene, the archetype of the metallocenes, came into use with the emergence of a new chemistry focused on electronic delocalization, supplanting the previous narrow focus on the oxidation of ferrocene to ferricenium, a compound that is unstable in aqueous media and has little biological activity [ 7 , 10 , 11 ]. In this context, the ferrocifens and ferrociphenols represent remarkable examples of biological efficacy, enabled by our understanding of their chemical mechanism of action in biological settings [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

et al. 2022

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SuccFerr (N-[4-ferrocenyl,5-5-bis (4-hydroxyphenyl)-pent-4-enyl]-succinimide) has remarkable antiproliferative effects in vitro, attributed to the formation of a stabilized quinone methide. The present article reports in vivo results for a possible preclinical study. SuccFerr is lipophilic and insoluble in water, so the development of a formulation to obviate this inconvenience was necessary. This was achieved by complexation with randomly methylated cyclodextrins (RAMEßCDs). This supramolecular water-soluble system allowed the in vivo experiments below to proceed. Application of SuccFerr on the glioblastoma cancer cell line U87 indicates that it affects the cellular cycle by inducing a blockade at G0/G1 phase, linked to apoptosis, and another one at the S phase, associated with senescence. Using healthy Fischer rats, we show that both intravenous and subcutaneous SuccFerr: RAMEßCD administration at 5 mg/kg lacks toxic effects on several organs. To reach lethality, doses higher than 200 mg/kg need to be administered. These results prompted us to perform an ectopic in vivo study at 1 mg/kg i.v. ferrocidiphenol SuccFerr using F98 cells xenografted in rats. Halting of cancer progression was observed after six days of injection, associated with an immunological defense response linked to the active principle. These results demonstrate that the properties of the selected ferrocidiphenol SuccFerr transfer successfully to in vivo conditions, leading to interesting therapeutic perspectives based on this chemistry.

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Section: Introductionmentioning

confidence: 99%

Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

et al. 2022

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“…157 The presence of cytotoxic ferrocenyl groups in close vicinity to the nucleobase moiety has shown to impart antibacterial or anticancer activity. 158 Thus, in 2015, Skiba et al 159 chromone ring promoted the antitumor potential. 160 Thus structures of various new thiopyran analogs have been listed in Figure 17, accounting for their potent cytotoxic activity along with their SAR.…”

Section: Thiophenementioning

confidence: 99%

“…Ferrocenyl‐nucleobases are a new class of nucleoside‐related molecules that have been recently a subject of interest 157 . The presence of cytotoxic ferrocenyl groups in close vicinity to the nucleobase moiety has shown to impart antibacterial or anticancer activity 158 . Thus, in 2015, Skiba et al 159 synthesized 113 and 114 by a hetero‐Diels–Alder cycloaddition reaction.…”

Section: Introductionmentioning

confidence: 99%

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

Laxmikeshav

Kumari

Shankaraiah

2021

Medicinal Research Reviews

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This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six-and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five-and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

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“…9,10 The exact mechanism of their antiproliferative action is still not fully understood, however, ROS (reactive oxygen species) generation has been proposed. 9,11 One of the distinguishing features of malignant cells is the enhanced production of reactive oxygen species (ROS) that makes them more vulnerable to oxidative stress. Since the ferrocene structure exists in a state of redox equilibrium, it can elicit ROS formation under physiological conditions and induce oxidative damage to DNA and protein biostructures.…”

Section: Introductionmentioning

confidence: 99%

Ferrocene modified analogues of imatinib and nilotinib as potent anti-cancer agents

et al. 2023

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Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action

Cited by 33 publications

References 32 publications

Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

Ferrocene modified analogues of imatinib and nilotinib as potent anti-cancer agents

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