Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity

Fabijańska, Małgorzata; Kasprzak, Maria; Ochocki, Justyn

doi:10.3390/ijms22147568

Cited by 11 publications

(8 citation statements)

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“…Ru(II) complexes with biologically active aminoflavone ligands [ 71 ] were synthesized in order to overcome cisplatin resistance in a number of cell lines. The compounds ( Figure 18 ) were tested against A2780, A2780cis, Toledo and Toledo-cis.…”

Section: Novel Metal Complexes In Cancer Therapymentioning

confidence: 99%

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Todorov

Kostova

2023

Molecules

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Since the accidental discovery of the anticancer properties of cisplatin more than half a century ago, significant efforts by the broad scientific community have been and are currently being invested into the search for metal complexes with antitumor activity. Coordination compounds of transition metals such as platinum (Pt), ruthenium (Ru) and gold (Au) have proven their effectiveness as diagnostic and/or antiproliferative agents. In recent years, experimental work on the potential applications of elements including lanthanum (La) and the post-transition metal gallium (Ga) in the field of oncology has been gaining traction. The authors of the present review article aim to help the reader “catch up” with some of the latest developments in the vast subject of coordination compounds in oncology. Herewith is offered a review of the published scientific literature on anticancer coordination compounds of Pt, Ru, Au, Ga and La that has been released over the past three years with the hope readers find the following article informative and helpful.

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Section: Novel Metal Complexes In Cancer Therapymentioning

confidence: 99%

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Todorov

Kostova

2023

Molecules

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“…Among the structural modifications operated on flavonoids, the introduction of amino groups at the flavone scaffold was one of the most frequent [29][30][31][32]. For example, flavone derivatives bearing amino groups were studied as anticancer compounds [33][34][35][36].…”

Section: Synthesis Of 5-and 7-aminoflavonesmentioning

confidence: 99%

Diversity-Oriented Synthesis: Amino Acetophenones as Building Blocks for the Synthesis of Natural Product Analogs

2021

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Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy in organic synthesis and is fully integrated in various drug discovery processes. On the other hand, natural products with multiple relevant pharmacological properties have been extensively investigated as scaffolds for ligand-based drug design. In this article, we report the amino dimethoxyacetophenones that can be easily synthesized and scaled up from the commercially available 3,5-dimethoxyaniline as valuable starting blocks for the DOS of natural product analogs. More focus is placed on the synthesis of analogs of flavones, coumarins, azocanes, chalcones, and aurones, which are frequently studied as lead compounds in drug discovery.

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“…One of the most important factors in the advancement of medicinal inorganic chemistry is still the widespread use of cisplatin and other platinum-based metallodrugs as chemotherapeutic agents against various cancers, including those of the ovary, bladder, and testicles [ 1 , 2 , 3 , 4 ]. In the search for coordination compounds that are toxic-free compared to cisplatin and effective against tumors, ruthenium compounds show the most promise due to their biological properties, which differ greatly from those of traditional platinum compounds in terms of their mechanism of action, toxicity, and biodistribution, and some ruthenium compounds have been shown to be quite selective for cancer cells [ 5 , 6 , 7 , 8 ]. It is widely known that ruthenium complexes have a strong affinity for cancer tissues and a reduced general toxicity when they bind to biological molecules such as DNA, making them potential candidates for anticancer drugs [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

et al. 2023

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This work aimed to evaluate in vitro DNA binding mechanistically of cationic nitrosyl ruthenium complex [RuNOTSP]+ and its ligand (TSPH2) in detail, correlate the findings with cleavage activity, and draw conclusions about the impact of the metal center. Theoretical studies were performed for [RuNOTSP]+, TSPH2, and its anion TSP−2 using DFT/B3LYP theory to calculate optimized energy, binding energy, and chemical reactivity. Since nearly all medications function by attaching to a particular protein or DNA, the in vitro calf thymus DNA (ctDNA) binding studies of [RuNOTSP]+ and TSPH2 with ctDNA were examined mechanistically using a variety of biophysical techniques. Fluorescence experiments showed that both compounds effectively bind to ctDNA through intercalative/electrostatic interactions via the DNA helix’s phosphate backbone. The intrinsic binding constants (Kb), (2.4 ± 0.2) × 105 M−1 ([RuNOTSP]+) and (1.9 ± 0.3) × 105 M−1 (TSPH2), as well as the enhancement dynamic constants (KD), (3.3 ± 0.3) × 104 M−1 ([RuNOTSP]+) and (2.6 ± 0.2) × 104 M−1 (TSPH2), reveal that [RuNOTSP]+ has a greater binding propensity for DNA compared to TSPH2. Stopped-flow investigations showed that both [RuNOTSP]+ and TSPH2 bind through two reversible steps: a fast second-order binding, followed by a slow first-order isomerization reaction via a static quenching mechanism. For the first and second steps of [RuNOTSP]+ and TSPH2, the detailed binding parameters were established. The total binding constants for [RuNOTSP]+ (Ka = 43.7 M−1, Kd = 2.3 × 10−2 M−1, ΔG0 = −36.6 kJ mol−1) and TSPH2 (Ka = 15.1 M−1, Kd = 66 × 10−2 M, ΔG0 = −19 kJ mol−1) revealed that the relative reactivity is approximately ([RuNOTSP]+)/(TSPH2) = 3/1. The significantly negative ΔG0 values are consistent with a spontaneous binding reaction to both [RuNOTSP]+ and TSPH2, with the former being very favorable. The findings showed that the Ru(II) center had an effect on the reaction rate but not on the mechanism and that the cationic [RuNOTSP]+ was a more highly effective DNA binder than the ligand TSPH2 via strong electrostatic interaction with the phosphate end of DNA. Because of its higher DNA binding affinity, cationic [RuNOTSP]+ demonstrated higher cleavage efficiency towards the minor groove of pBR322 DNA via the hydrolytic pathway than TSPH2, revealing the synergy effect of TSPH2 in the form of the complex. Furthermore, the mode of interaction of both compounds with ctDNA has also been supported by molecular docking.

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Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity

Cited by 11 publications

References 50 publications

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Diversity-Oriented Synthesis: Amino Acetophenones as Building Blocks for the Synthesis of Natural Product Analogs

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

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