Ferrocenes in medicinal chemistry; a personal perspective

Sansook, Supojjanee; Hassell-Hart, Storm; Ocasio, Cory A.; Spencer, John

doi:10.1016/j.jorganchem.2019.121017

Cited by 55 publications

(25 citation statements)

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“…A variety of monoiron complexes have been assessed for the anticancer potential both in vitro and in vivo [ 19 , 20 , 21 , 22 ]. Following the successful experience with ferroquine, a conjugate between ferrocene and the drug chloroquine, which entered phase II clinical trials as an antimalarial agent ( Figure 1 , structure I ) [ 4 , 23 , 24 ], the anticancer properties of related ferrocene derivatives have been intensively investigated (an example in Figure 1 , structure II ) [ 25 , 26 , 27 , 28 ]. This family of compounds exhibits a substantial robustness supplied by the ferrocene skeleton and exerts a cytotoxic activity essentially by unbalancing cellular redox homeostasis via iron(II) to iron(III) oxidation [ 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

et al. 2021

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A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R′)C(R″)CN(R)(Y)}]CF3SO3 (2–7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69–95% yields from the reactions of diiron μ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R′ = R″ = Me) and 3a (R = CH2CH=CH2, Y = R′ = Me, R″ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV–Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol–water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2–7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R′ = R″ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).

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Section: Introductionmentioning

confidence: 99%

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

et al. 2021

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“…55,56 Motivated by the promising results obtained from the ferrocenyl derivatization of organic drugs such as tamoxifen and chloroquine to give ferrocifen and ferroquine, respectively, we envisaged applying the same concept to fight fungal infections. 32,49,[57][58][59] Fluconazole has been chosen as the parent drug because of its broad spectrum applications (e.g. systemic and topic administration, active against a large number of mycoses).…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

In vivo active organometallic-containing antimycotic agents

et al. 2021

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“…Ferrocene derivatives are becoming more and more popular in medicinal molecules due to their unique chemical structures, biological activities, low toxicity, and reversible redox behavior [ 6 ]. Some compounds were found to exhibit a variety of pharmacological properties, including antibacterial [ 7 ], antimalarial [ 8 ], antifungal [ 9 ], antiviral [ 10 ], and anticancer activities [ 11 ]. Fortunately, we have successfully developed novel protocols to build a series of ferrocene derivatives based on transition metal-catalyzed C-H functionalization [ 12 ], and have explored the bioactivities of ferrocenyl olefins [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma

Zheng

Zeng

Tang

et al. 2021

IJMS

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In this study, detailed information on hepatocellular carcinoma (HCC) cells (HepG-2, SMMC-7721, and HuH-7) and normal human liver cell L02 treated by ferrocene derivatives (compounds 1, 2 and 3) is provided. The cell viability assay showed that compound 1 presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound 1 was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound 1 could induce apoptosis in HCC cells by loss of mitochondrial membrane potential (ΔΨm), accumulation of reactive oxygen species (ROS), decrease in Bcl-2, increase in BAX and Bad, translocation of Cytochrome c, activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound 1 would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.

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Ferrocenes in medicinal chemistry; a personal perspective

Abstract: We present a short review of some of our recent work mainly targeting cancer-related oncoproteins through the development of primarily novel air-and water-stable ironbased organometallic agents. This work was presented at the recent ISBOMC19 conference at York as an invited lecture.

Cited by 55 publications

References 55 publications

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

In vivo active organometallic-containing antimycotic agents

Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma

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