Organotin complexes containing carboxylate ligands with maleimide and naphthalimide derived partial structures: TrxR inhibition, cytotoxicity and activity in resistant cancer cells

Oliveira, Kely Navakoski de; Andermark, Vincent; Onambele, Liliane A.; Dahl, Gregor; Prokop, Aram; Ott, Ingo

doi:10.1016/j.ejmech.2014.09.075

Cited by 37 publications

(10 citation statements)

References 26 publications

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“…Among them, the di‐ n ‐butyltin (IV) complexes 158–164 (Figure ) were active against purified enzyme with IC 50 values in the range of 2 to 13 μM (Table ). Derivatives 160 and 161 were the most active compounds (IC 50 values of 2.50 and 2.30 μM, respectively) …”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

133

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Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.

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Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

133

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“…Subsequently, the same authors prepared a series of organotin(IV) carboxylate complexes 128 – 139 (Figure 7) with naphthalimide-, citraconimide- or maleimide-derived ligands. As TrxR inhibitors, three of the four newly prepared maleimide derivatives were more effective compared with both citraconimide- and naphthalimide-containing compounds, eliciting IC 50 values in the 2.3–11.3 µM range [89]. Even though all of these compounds showed a TrxR inhibitory activity at µM concentrations and some SARs were tentatively drawn, again, no clear correlation was established between TrxR inhibition and cytotoxicity potency, thus indicating that inhibition of TrxR is unlikely the main mode of action of these compounds.…”

Section: Other Metal-containing Inhibitorsmentioning

confidence: 99%

Metal- and Semimetal-Containing Inhibitors of Thioredoxin Reductase as Anticancer Agents

Gandin

Fernandes

2015

Molecules

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Abstract:The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox homeostasis and signaling pathways. Recently, these selenoproteins have emerged as promising therapeutic targets for anticancer drug development, often being overexpressed in tumor cells and contributing to drug resistance. Herein, we summarize the current knowledge on metal-and semimetal-containing molecules capable of hampering mammalian TrxRs, with an emphasis on compounds reported in the last decade.

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“…Inhibition of topoisomerases, especially topoisomerase II (Topo II) has been proposed as the major mechanism by which naphthalimides induce cell cycle arrest and apoptosis in cancer cells [11]. Other mechanisms have also been suggested to be involved in the anticancer effects of naphthalimides, including inhibition of histone deacetylase [12], DNA and RNA synthesis [13], receptor tyrosine kinases [14], NF-κB signaling [14], poly(ADP-ribose) polymerase-1(PARP-1) [15], thioredoxin reductase (TrxR) [16], restoration of the functions of p53 and p21 [17], induction of ROS and malfunction of lysosome and mitochondria [17–19]. However, the exact mechanisms by which naphthalimides impact cellular physiological processes remain largely in vague, and lack of detailed mechanistic information further dampened the attempts to improve the therapeutic efficacy and toxicological profiles of naphthalimides.…”

Section: Introductionmentioning

confidence: 99%

A novel triazolonaphthalimide induces apoptosis and inhibits tumor growth by targeting DNA and DNA-associated processes

Yang

et al. 2017

Oncotarget

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DNA and DNA-associated processes have been classes of the most important targets of chemotherapeutic drugs. As classic DNA intercalators and topoisomerase inhibitors, naphthalimides have been extensively investigated as potential anti-cancer drugs. We recently synthesized a novel series of triazolonaphthalimides with excellent anti-cancer activities. In the present study, one of the most potent triazolonaphthalimides, LSS-11, was investigated. LSS-11 bound to DNA in vitro and in cell mainly by minor groove binding and significantly increased the stability of DNA, which could be fundamental for the biological activities of LSS-11. In addition to inhibiting DNA topoisomerase II-catalyzed decatenation of knotted circulated DNA, LSS-11 dramatically inhibited DNA replication mediated by polymerase chain reaction and isothermal helicase-dependent amplification, as well as the expression of luciferase driven by a minimal TA promoter in cell. Furthermore, LSS-11 exhibited strong cytotoxicity in selected human colon cancer cell lines by inducing cell cycle arrest and apoptosis, which was accompanied by DNA damage response. Finally, LSS-11 potently inhibited the growth of S180 murine sarcoma and SW480 human colorectal cancer xenografts in vivo without significant major toxicities. These results suggest that LSS-11 deserves further research and development as a novel anti-cancer agent, and provided new understandings of mechanisms by which LSS-11 inhibited multiple DNA-associated processes and tumor growth.

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Organotin complexes containing carboxylate ligands with maleimide and naphthalimide derived partial structures: TrxR inhibition, cytotoxicity and activity in resistant cancer cells

Cited by 37 publications

References 26 publications

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Metal- and Semimetal-Containing Inhibitors of Thioredoxin Reductase as Anticancer Agents

A novel triazolonaphthalimide induces apoptosis and inhibits tumor growth by targeting DNA and DNA-associated processes

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