Transcription Inhibition by Organometallic Ruthenium - Arene Anticancer Complexes in Live Mammalian Cells

2012 ◽  
Vol 65 (9) ◽  
pp. 1271 ◽  
Author(s):  
Astrid Astarina ◽  
Mun Juinn Chow ◽  
Wee Han Ang
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Transcription Inhibition ◽  
Biological Targets ◽  
Arene Ligands ◽  
Arene Ligand ◽  
Anticancer Complexes ◽  
Covalent Adducts ◽  
The Spectator ◽  
Ruthenium Arene

Organometallic ruthenium–arene RAPTA complexes, currently being actively pursued as potential anticancer agents, interact with intracellular biological targets to form covalent adducts. Because their mode of action is still unclear, we investigated their binding with DNA and the ability of ruthenated-DNA adducts to elicit cellular responses such as transcription inhibition and repair. To investigate the influence of the spectator arene ligands on RAPTA activity, a novel RAPTA complex containing the bulky 1,3,5-triisopropylbenzene ligand was synthesized and characterized. Transcription experiments carried out in live mammalian cells using ruthenated plasmid probes revealed that increasing steric bulk of the arene ligand did not improve its ability to arrest transcription.

scholarly journals Activity of Indenoisoquinolines against African Trypanosomes

2008 ◽  
Vol 53 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Rahul P. Bakshi ◽  
Dongpei Sang ◽  
Andrew Morrell ◽  
Mark Cushman ◽  
Theresa A. Shapiro
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Sleeping Sickness ◽  
Water Soluble ◽  
African Trypanosomes ◽  
In Vivo Experiments ◽  
Topoisomerase Ib ◽  
Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

Rhodamine-modified fluorescent half-sandwich iridium and ruthenium complexes: potential application as bioimaging and anticancer agents

2019 ◽  
Vol 48 (15) ◽  
pp. 4788-4793 ◽  
Author(s):  
Wenli Ma ◽  
Lihua Guo ◽  
Zhenzhen Tian ◽  
Shumiao Zhang ◽  
Xiangdong He ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Potential Application ◽  
Ruthenium Complexes ◽  
Anticancer Complexes ◽  
Half Sandwich

Most half-sandwich metal anticancer complexes are non-fluorescent, which results in an uncertain mechanism of action (MoA).

scholarly journals Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

2020 ◽  
Vol 21 (22) ◽  
pp. 8692
Author(s):  
Alessandra Benassi ◽  
Filippo Doria ◽  
Valentina Pirota
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Properties ◽  
Aromatic Rings ◽  
Antitumor Effects ◽  
Comprehensive Overview ◽  
Biological Targets ◽  
Structural Modifications ◽  
Starting Point ◽  
Oxadiazole Derivatives

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

Ruthenium Arene Anticancer Complexes

2006 ◽  
pp. 39-64 ◽  
Author(s):  
Michael Melchart ◽  
Peter J. Sadler
Keyword(s):  
Anticancer Complexes ◽  
Ruthenium Arene

Theoretical view on a linear end-on manganese–dioxygen complex bearing a calix[4]arene ligand

RSC Advances ◽  
2016 ◽  
Vol 6 (85) ◽  
pp. 81517-81526 ◽  
Author(s):  
Xiang-Cui Huang ◽  
Hui-Fang Wang ◽  
Jian-Ping Lang
Keyword(s):  
Dft Calculations ◽  
Solvent Polarity ◽  
Arene Ligands ◽  
Theoretical View ◽  
Arene Ligand ◽  
Size Adjustment

The Mn–O–O angle of mononuclear manganese(iii)-superoxo complexes supported by zwitterionic calix[4]arene ligands can be modulated via solvent polarity perturbations and/or ligand size adjustment as indicated by DFT calculations.

scholarly journals Thiadiazole derivatives as anticancer agents

2020 ◽  
Vol 72 (5) ◽  
pp. 1079-1100 ◽  
Author(s):  
Monika Szeliga
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Cellular Membrane ◽  
Biological Targets ◽  
Cancer Pathogenesis ◽  
Thiadiazole Ring ◽  
Substantial Progress ◽  
Thiadiazole Derivatives

Abstract In spite of substantial progress made toward understanding cancer pathogenesis, this disease remains one of the leading causes of mortality. Thus, there is an urgent need to develop novel, more effective anticancer therapeutics. Thiadiazole ring is a versatile scaffold widely studied in medicinal chemistry. Mesoionic character of this ring allows thiadiazole-containing compounds to cross cellular membrane and interact strongly with biological targets. Consequently, these compounds exert a broad spectrum of biological activities. This review presents the current state of knowledge on thiadiazole derivatives that demonstrate in vitro and/or in vivo efficacy across the cancer models with an emphasis on targets of action. The influence of the substituent on the compounds’ activity is depicted. Furthermore, the results from clinical trials assessing thiadiazole-containing drugs in cancer patients are summarized.

scholarly journals Multivalent Carbonic Anhydrases Inhibitors

2019 ◽  
Vol 20 (21) ◽  
pp. 5352 ◽  
Author(s):  
Fabrizio Carta ◽  
Pascal Dumy ◽  
Claudiu T. Supuran ◽  
Jean-Yves Winum
Keyword(s):  
Anticancer Agents ◽  
Drug Targets ◽  
Diagnostic Tools ◽  
Biomolecular Recognition ◽  
Carbonic Anhydrases ◽  
Biological Targets ◽  
Processing Enzymes ◽  
Zinc Metalloenzymes ◽  
Antiglaucoma Agents ◽  
Isoform Selectivity

Biomolecular recognition using a multivalent strategy has been successfully applied, this last decade on several biological targets, especially carbohydrate-processing enzymes, proteases, and phosphorylases. This strategy is based on the fact that multivalent interactions of several inhibitory binding units grafted on a presentation platform may enhance the binding affinity and selectivity. The zinc metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are considered as drug targets for several pathologies, and different inhibitors found clinical applications as diuretics, antiglaucoma agents, anticonvulsants, and anticancer agents/diagnostic tools. Their main drawback is related to the lack of isoform selectivity leading to serious side effects for all pathologies in which they are employed. Thus, the multivalent approach may open new opportunities in the drug design of innovative isoform-selective carbonic anhydrase inhibitors with biomedical applications.

Organometallic Chemistry, Biology and Medicine: Ruthenium Arene Anticancer Complexes

ChemInform ◽  
2006 ◽  
Vol 37 (4) ◽  
Author(s):  
Yaw Kai Yan ◽  
Michael Melchart ◽  
Abraha Habtemariam ◽  
Peter J. Sadler
Keyword(s):  
Organometallic Chemistry ◽  
Anticancer Complexes ◽  
Ruthenium Arene
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