Recent advances and application of ruthenium complexes in tumor malignancy

Kanaoujiya, Rahul; Meenakshi, .; Srivastava, Shekhar; Singh, Rasmeet; Mustafa, Ghulam

doi:10.1016/j.matpr.2022.07.098

Cited by 27 publications

(14 citation statements)

References 63 publications

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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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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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“… 5 − 7 The efficiency of metal-based drugs in cancer therapy cannot be underestimated, as it has recently been used in about 32 out of 78 cancer regimens. 8 Despite these spectacular attributes found in metal-based complexes, they have certain disadvantages as it causes toxic side effects and displays chemotherapeutic resistance. 9 , 10 Various studies on the transition metal rhenium (Re) have been conducted in recent years to develop novel anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

“…This success is exemplified by the discovery of cisplatin in 1960 by Barnett Rosenberg . Significantly, it has also conceptualized the modern era of metal-based anticancer drugs, like cisplatin, carboplatin, and oxaliplatin. , In recent years, investigations were carried out with the commitment of researchers and scientists to develop a new anticancer drug consisting of a range of different complexes emanating from Re, Au, Pd, Rh, Os, and Ir metal complexes. − The efficiency of metal-based drugs in cancer therapy cannot be underestimated, as it has recently been used in about 32 out of 78 cancer regimens . Despite these spectacular attributes found in metal-based complexes, they have certain disadvantages as it causes toxic side effects and displays chemotherapeutic resistance. , Various studies on the transition metal rhenium (Re) have been conducted in recent years to develop novel anticancer agents. − Syntheses were carried out on many rhenium complexes, exploring their potential properties as an anticancer agent due to their biological activity of cytotoxicity .…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activities of Re(I) Tricarbonyl and Its Imidazole-Based Ligands: Insight from a Theoretical Approach

et al. 2023

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Rhenium complexes have been observed experimentally to exhibit good inhibitory activity against malignant cells. Hence, our motivation is to explore this activity from a theoretical perspective. In the present study, density functional theory (DFT) and in silico molecular docking approaches were utilized to unravel the unique properties of metal-based rhenium tricarbonyl complexes as effective anticancer drugs. All DFT calculations and geometric optimizations were conducted using the well-established hybrid functional B3LYP-GD(BJ)/Gen/6-311++G(d,p)/ LanL2DZ computational method. The FT-IR spectroscopic characterization of the complexes:R7), and fac-[Re(Tfpc)(CO) 3 (Im)] (R8) was explored. To gain insights into the electronic structural properties, bioactivity, and stability of these complexes, the highest occupied molecular orbital−lowest unoccupied molecular orbital analysis, binding energy, and topological analysis based on quantum theory of atoms-in-molecules were considered. The anticancer activities of the complexes were measured via in silico molecular docking against human BCL-2 protein (IG5M) and proapoptotic (agonist) BAX 1 protein (450O). The results showed that the studied complexes exhibited good binding affinity (−3.25 to −10.16 kcal/mol) and could cause significant disruption of the normal physiological functions of the studied proteins. The results of DFT calculations also showed that the studied complexes exhibited good stability and are suitable candidates for the development of anticancer agents.

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“…They also reported the recent advancement of these lignad base chemistry domain and its future prospect as a potential bioactive core [ 87 ]. In 2022, Kanaoujiya et al also reported a review exploring the role of ruthenium-based complexes for the treatment of malignant tumors [ 88 ]. Mikhailov reviewed the role of aza, oxa-aza and thia-aza macrocyclic transition metal complexes in gelatin matrix [ 89 ].…”

Section: Introductionmentioning

confidence: 99%

Review on Isatin- A Remarkable Scaffold for Designing Potential Therapeutic Complexes and Its Macrocyclic Complexes with Transition Metals

Bugalia,

Dhayal,

Sachdeva

et al. 2023

J Inorg Organomet Polym

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Role of synthetic coordination chemistry in pharmaceutical science is expeditiously increased due to its sundry relevances in this field. The present review endows the synthesized macrocyclic complexes of transition metal ions containing isatin and its derivatives as ligand precursors, their characterization and their copious pharmaceutical applications. Isatin (1 H -Indole-2,3-dione) is a protean compound (presence of lactam and keto moiety permits to change its molecular framework) that can be obtained from marine animals, plants, and is also found in mammalian tissues and in human fluids as a metabolite of amino acids. It can be used for the synthesis of miscellaneous organic and inorganic complexes and for designing of drugs since it has remarkable utility in pharmaceutical industry due to its wide range of biological and pharmacological activities, for instance anti-microbial, anti-HIV, anti-tubercular, anti-cancer, anti-viral, anti-oxidant, anti-inflammatory, anti-angiogenic, analgesic activity, anti-Parkinson’s disease, anti-convulsant etc. This review provides extensive information about the latest methods for the synthesis of isatin or its substituted derivatives based macrocyclic complexes of transition metals and their plentiful applications in medicinal chemistry. Graphical Abstract

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Recent advances and application of ruthenium complexes in tumor malignancy

Cited by 27 publications

References 63 publications

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

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

Anticancer Activities of Re(I) Tricarbonyl and Its Imidazole-Based Ligands: Insight from a Theoretical Approach

Review on Isatin- A Remarkable Scaffold for Designing Potential Therapeutic Complexes and Its Macrocyclic Complexes with Transition Metals

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