Click ferrocenyl-erlotinib conjugates active against erlotinib-resistant non-small cell lung cancer cells in vitro

Biegański, Przemysław; Godel, Martina; Riganti, Chiara; Kawano, Daniel Fábio; Kopecka, Joanna; Kowalski, Konrad

doi:10.1016/j.bioorg.2021.105514

Cited by 17 publications

(28 citation statements)

References 78 publications

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“…Free radicals are key cell-damage causative agents that are often generated by ferrocenium species inside cancer cells. 27 , 31 , 59 − 61 It was therefore justified to check whether our compounds are also capable of free-radical generation. In this regard, 5,5-dimethyl-1-pyrroline N -oxide (DMPO) was used as a spin trap.…”

Section: Resultsmentioning

confidence: 99%

“…16 , 61 Oxidative stress (OS) resulting from ROS production is an important factor that takes part in the anticancer activity of organometallic compounds. 27 , 31 , 59 , 60 Concerning that, the aim of the following studies was to examine whether studied compounds generate ROS in cancer cells and how the viability of the treated cells changes in the presence of N -acetyl cysteine (NAC) free-radical scavenger. 96 Thus, we investigated the amount of ROS (OH • , O2 •– , H 2 O 2 , ROO • ) produced by compounds 1a and 1c and reference drugs at 20 μM concentration and 1 h treatment time in H1975 and A549 cells.…”

Section: Resultsmentioning

confidence: 99%

“… 64 − 68 In regard to biological applications, 1,2,3-triazoles have proved their value as easy-to-synthesize linkers in bioconjugate chemistry. 30 , 31 , 64 , 68 In this work, another leap forward has been taken with respect to biological applications of 1,2,3-triazoles as they have been used not only as linkers but also as entities that allow electron transfer between two ferrocenyl groups to occur. The selection of 3′-azido-3′-deoxythymidine (AZT) as the source material for compounds 1a – c was motivated by the biological significance of deoxythymidine nucleoside and general importance of CuAAC reactions in nucleic acid chemistry and biology.…”

Section: Introductionmentioning

confidence: 99%

“…Reported in 1951, ferrocene (FcH = Fe(η 5 -C 5 H 5 ) 2 ) has become a cornerstone of modern organometallic chemistry. , In the last 71 years, ferrocenyl (Fc) compounds have found many applications in catalysis, biology, materials chemistry, and so forth. − One of the reasons behind this success is due to the electrochemical properties of ferrocene and its derivatives. The Fc/[Fc] + redox couple is usually characterized by superb chemical reversibility combined with great thermal stability .…”

Section: Introductionmentioning

confidence: 99%

“…The common feature of 1a – c and 2a – c series of compounds is that they contain the 1,2,3-triazole structural motif. Due to the development of the copper-catalyzed 1,3-dipolar azide–alkyne cycloaddition (CuAAC) reaction, , the interest in the chemistry of 1,2,3-triazoles has increased greatly in the recent time. − In regard to biological applications, 1,2,3-triazoles have proved their value as easy-to-synthesize linkers in bioconjugate chemistry. ,,, In this work, another leap forward has been taken with respect to biological applications of 1,2,3-triazoles as they have been used not only as linkers but also as entities that allow electron transfer between two ferrocenyl groups to occur. The selection of 3′-azido-3′-deoxythymidine (AZT) as the source material for compounds 1a – c was motivated by the biological significance of deoxythymidine nucleoside and general importance of CuAAC reactions in nucleic acid chemistry and biology. , Taking into account the above motivation, compounds 1a and 2a as well as their mononuclear analogues 1c and 2c were used to study their anticancer activity in human A549 and H1975 non-small-cell lung cancer (NSCLC) cells and nonmalignant bronchial epithelium BEAS-2B cells.…”

Section: Introductionmentioning

confidence: 99%

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Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

et al. 2022

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Mixed-valence (MV) binuclear ferrocenyl compounds have long been studied as models for testing theories of electron transfer and in attempts to design molecular-scale electronic devices ( e.g ., molecular wires). In contrary to that, far less attention has been paid to MV binuclear ferrocenes as anticancer agents. Herein, we discuss the synthesis of six 1,2,3-triazole ferrocenyl compounds for combined (spectro)electrochemical, electron paramagnetic resonance (EPR), computational, and anticancer activity studies. Our synthetic approach was based on the copper-catalyzed 1,3-dipolar azide–alkyne cycloaddition reaction and enabled us to obtain in one step compounds bearing either one, two, or three ferrocenyl entities linked to the common 1,2,3-triazole core. Thus, two series of complexes were obtained, which pertain to derivatives of 3′-azido-3′-deoxythymidine (AZT) and 3-azidopropionylferrocene, respectively. Based on the experimental and theoretical data, the two mono-oxidized species corresponding to binuclear AZT and trinuclear 3-azidopropionylferrocene complexes have been categorized as class II mixed-valence according to the classification proposed by Robin and Day. Of importance is the observation that these two compounds are more active against human A549 and H1975 non-small-cell lung cancer cells than their congeners, which do not show MV characteristics. Moreover, the anticancer activity of MV species competes or surpasses, dependent on the cell line, the activity of reference anticancer drugs such as cisplatin, tamoxifen, and 5-fluorouracil. The most active from the entire series of compounds was the binuclear thymidine derivative with the lowest IC 50 value of 5 ± 2 μM against lung H1975 cancer cells. The major mechanism of antiproliferative activity for the investigated MV compounds is based on reactive oxygen species generation in cancer cells. This hypothesis was substantiated by EPR spin-trapping experiments and the observation of decreased anticancer activity in the presence of N -acetyl cysteine (NAC) free-radical scavenger.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

et al. 2022

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Metal complexes bearing EGFR‐inhibiting ligands as promising anticancer agents

Ma,

Wang,

et al. 2024

Medicinal Research Reviews

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Overexpression of the epidermal growth factor receptor (EGFR, erbB1) has been observed in a wide range of solid tumors and has frequently been associated with poor prognosis. As a result, EGFR inhibition has become an attractive anticancer drug design strategy, and a large number of small molecular inhibitors have been developed. Despite the widespread clinical use of EGFR tyrosine kinase inhibitors (TKIs), their drug resistance, inadequate accumulation in tumors, and severe side effects have spurred the search for better antitumor drugs. Metal complexes have attracted much attention because of their different mechanisms compared with EGFR‐TKIs. Therefore, the combination of metals and inhibitors is a promising anticancer strategy. For example, Ru and Pt centers are introduced to design complexes with double or multiple targets, while Au complexes are combined with inhibitors to overcome drug resistance. Co complexes are designed as prodrugs with weak side effects and enhanced targeting by the hypoxia activation strategy, and other metals such as Rh and Fe enhance the anticancer effect of the complexes. In addition, the introduction of Ga center is beneficial to the development of nuclear imaging tracers. In this paper, metal EGFR‐TKI complexes in the last 15 years are reviewed, their mechanisms are briefly introduced, and their advantages are summarized.

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Ferrocenyl Azoles: Versatile N‐Containing Heterocycles and their Anticancer Activities

Sadanala,

Trivedi

2024

The Chemical Record

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The medicinal chemistry of ferrocene has gained its momentum after the discovery of biological activities of ferrocifen and ferroquine. These ferrocenyl drugs have been designed by replacing the aromatic moiety of the organic drugs, tamoxifen and chloroquine respectively, with a ferrocenyl unit. The promising biological activities of these ferrocenyl drugs have paved a path to explore the medicinal applications of several ferrocenyl conjugates. In these conjugates, the ferrocenyl moiety has played a vital role in enhancing or imparting the anticancer activity to the molecule. The ferrocenyl conjugates induce the cytotoxicity by generating reactive oxygen species and thereby damaging the DNA. In medicinal chemistry, the five membered nitrogen heterocycles (azoles) play a significant role due to their rigid ring structure and hydrogen bonding ability with the biomolecules. Several potent drug candidates with azole groups have been in use as chemotherapeutics. Considering the importance of ferrocenyl moiety and azole groups, several ferrocenyl azole conjugates have been synthesized and screened for their biological activities. Hence, in the view of a wide scope in the development of potent drugs based on ferrocenyl azole conjugates, herein we present the details of synthesis and the anticancer activities of ferrocenyl compounds bearing azole groups such as imidazole, triazoles, thiazole and isoxazoles.

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Click ferrocenyl-erlotinib conjugates active against erlotinib-resistant non-small cell lung cancer cells in vitro

Cited by 17 publications

References 78 publications

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

Metal complexes bearing EGFR‐inhibiting ligands as promising anticancer agents

Ferrocenyl Azoles: Versatile N‐Containing Heterocycles and their Anticancer Activities

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