Photoinduced Electron-Transfer Reactions of Carbonic Anhydrase Inhibitor Containing Tris(2,2′-bipyridine)ruthenium(II) Analogue

Takashima, Hiroshi; Fukuda, Michinari; Nakagaki, Fumie; Ogata, Tomoko; Tsukahara, Keiichi

doi:10.1021/jp310604w

Cited by 5 publications

(7 citation statements)

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“…Moving away from the ruthenocene framework, Tsukahara, Takashima, et al developed a ruthenium(II)-bipy complex tethered to a benzenesulfonamide moiety, (286), Figure 69. 448 The team investigated the CA inhibition activity of this complex and found it to have comparable activity relative to commercially available CA inhibitors. While the complex was not designed to be "multitargeted", extensive photophysical and kinetic studies associated with this complex were described.…”

Section: Chemical Reviewsmentioning

confidence: 99%

Toward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?

2019

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While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we are moving from a single- toward a multitargeted approach. This approach lies at the very heart of medicinal inorganic chemistry. In this review, we have endeavored to showcase how a “multitargeted” approach to drug design has led to new families of metallodrugs which may not only reduce systemic toxicities associated with modern day chemotherapeutics but also address resistance issues that are plaguing many chemotherapeutic regimens. We have focused our attention on metallodrugs incorporating platinum and ruthenium ions given that complexes containing these metal ions are already in clinical use or have advanced to clinical trials as anticancer agents. The “multitargeted” complexes described herein not only target DNA but also contain either vectors to enable them to target cancer cells selectively and/or moieties that target enzymes, peptides, and intracellular proteins. Multitargeted complexes which have been designed to target the mitochondria or complexes inspired by natural product activity are also described. A summary of advances in this field over the past decade or so will be provided.

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Section: Chemical Reviewsmentioning

confidence: 99%

Toward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?

2019

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“…Acetazolamide, methazolamide, ethoxzolamide, saccharin, brinzolamide, and dorzolamide molecules inhibit CAs. , Among the various isoforms of CAs, it is now thought that CA IX and CA XII are two membrane-bound isoforms that help to control the pH of cancer cells in a hypoxic environment. Thus, hypoxia-inducible CA IX appears to be a promising target for anticancer therapy because of its overexpression in many cancer cells compared to normal cells. − The activity of CA targeting sulfonamides may be modified and improved upon binding to transition-metal ions. ,− It was recently shown that 4-(2-aminoethyl)benzenesulfonamide (AEBS)-bound gold nanoparticles selectivity target CA IX over CA I and CA II . Hence, sulfonamides have the scope to target cancer cells over normal cells selectively.…”

Section: Introductionmentioning

confidence: 99%

Effect of an Imidazole-Containing Schiff Base of an Aromatic Sulfonamide on the Cytotoxic Efficacy of N,N-Coordinated Half-Sandwich Ruthenium(II) p-Cymene Complexes

et al. 2021

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Sulfonamides have a broad range of therapeutic applications, which include the inhibition of various isoforms of carbonic anhydrases (CAs). Among the various CA isoforms, CA IX is overexpressed in tumors and regulates the pH of the tumor microenvironment. Herein we present five new ruthenium(II) p-cymene complexes (1−5) of Schiff base ligands (L1−L4) of 4-(2-aminoethyl)benzenesulfonamide by varying the aldehyde to enhance the selective cytotoxicity toward cancer cells. All of the complexes are stable to aquation for the observed period of 24 h except 1, which aquated within 1 h, but the monoaquated species is stable for 24 h. The two imidazole derivatives, 1 and 2, are cytotoxic to the cancer cells MDA-MB-231 and MIA PaCa-2 but not to the noncancerous cells CHO and MDCK. The enhanced toxicity in hypoxia against MDA-MB-231 may be due to the greater expression of CA IX in hypoxia, as per the immunofluorescence data. The most cytotoxic complexes, 1 and 2, are lipophilic, whereas 3−5 show high hydrophilicity and are not cytotoxic up to 200 μM. Complexes 1 and 2 also show a higher cellular accumulation in MDA-MB-231 than the nontoxic yet solution-stable complex 5. The cytotoxic complexes bind with the model nucleobase 9-ethylguanine but have slow reactivity toward cellular tripeptide glutathione. Both 1 and 2 induce apoptosis by depolarizing the mitochondrial membrane potential and arrest the cell cycle in the SubG1 phase.

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“…The second‐order rate constant, k q , for the initial step is also calculated to be 2.6 × 10 7 M −1 s −1 (Figure S4b). Then, the first‐order rate constant for the second step, k IET , is determined to be 8.9 × 10 5 s −1 ( τ 2 = 1.13 microseconds), which is faster than the previously reported one of [Ru(bpy) 2 (bpybs)]‐CA system ( k IET = 6.6 × 10 4 s −1 in Table ) . In the CA‐[Ru(bpydbs) 3 ] 2+ ‐[CoCl(NH 3 ) 5 ] 2+ system, the photoexcited state of 3 ([Ru(bpydbs) 3 ] 2+ )* was quenched by intermolecular ET most slowly (first step).…”

Section: Resultsmentioning

confidence: 99%

“…In order to investigate photoinduced reactions within CA matrices, we previously constructed a CA‐inhibitor complex by using a benzenesulfonamide group and a wire molecule . As the initial [Ru(bpy) 3 ] 2+ ‐based CA inhibitor, [Ru(bpy) 2 (bpybs)] 2+ {bpy = 2,2′‐bipyridine and bpybs = 4′‐methyl‐2,2′‐bipyridinyl‐4‐carboxylic acid (2‐{2‐[(4‐sulphamoylbenzoylamino)ethoxy]ethoxy}ethyl)amide} was prepared.…”

Section: Introductionmentioning

confidence: 99%

Photoinduced electron‐transfer reactions of tris(2,2′‐bipyridine)ruthenium(II)‐based carbonic anhydrase inhibitors tethering plural binding sites

Suwa

Imamura

Awano

et al. 2018

J of Physical Organic Chem

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Photoinduced Electron-Transfer Reactions of Carbonic Anhydrase Inhibitor Containing Tris(2,2′-bipyridine)ruthenium(II) Analogue

Cited by 5 publications

References 95 publications

Toward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?

Toward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?

Effect of an Imidazole-Containing Schiff Base of an Aromatic Sulfonamide on the Cytotoxic Efficacy of N,N-Coordinated Half-Sandwich Ruthenium(II) p-Cymene Complexes

Photoinduced electron‐transfer reactions of tris(2,2′‐bipyridine)ruthenium(II)‐based carbonic anhydrase inhibitors tethering plural binding sites

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