Mustards-Derived Terpyridine–Platinum Complexes as Anticancer Agents: DNA Alkylation vs Coordination

2021 ◽  
Vol 60 (4) ◽  
pp. 2414-2424
Author(s):  
Muneebah Adams ◽  
Matthew P. Sullivan ◽  
Kelvin K. H. Tong ◽  
David C. Goldstone ◽  
Muhammad Hanif ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Platinum Complexes ◽  
Dna Alkylation

Luminescent cyclometallated platinum(ii) complexes: highly promising EGFR/DNA probes and dual-targeting anticancer agents

2018 ◽  
Vol 5 (2) ◽  
pp. 413-424 ◽  
Author(s):  
Yang Zhang ◽  
Qun Luo ◽  
Wei Zheng ◽  
Zhaoying Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Platinum Complexes ◽  
Living Cells ◽  
Dna Probes ◽  
High Potential ◽  
Luminescent Probes ◽  
Dual Targeting

Cyclometallated platinum complexes bearing 4-anilinoquinazolines exhibit high potential as luminescent probes for EGFR/DNA in living cells and dual-targeting anticancer agents.

Advancements in the Use of Platinum Complexes as Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajiv Sharma ◽  
Vikram Jeet Singh ◽  
Pooja A Chawla
Keyword(s):  
Anticancer Agents ◽  
Biomedical Applications ◽  
Clinical Importance ◽  
Platinum Complexes ◽  
Water Soluble ◽  
Platinum Compounds ◽  
Anticancer Compounds ◽  
Cellular Resistance ◽  
Anti Cancer ◽  
Target Effects

Background: The platinum (II) complexes as anticancer agents have been well explored for the development of novel analogs. Yet, none of them achieved clinical importance in oncology. At present, anticancer compounds containing platinum (II) complexes have been employed in the treatment of colorectal, lung, and genitourinary tumors. Among the platinum-based anticancer drugs, Cisplatin (cis-diamine dichloroplatinum (II), cis-[Pt(NH3)2Cl2]) is one of the most potent components of cancer chemotherapy. The nephrotoxicity, neurotoxicity and ototoxicity, and platinum compounds associated resistant cancer are some major disadvantages. Objective: With the rapidly growing interest in platinum (II) complexes in tumor chemotherapy, researchers have synthesized many new platinum analogs as anticancer agents that show better cytotoxicity, and less off-target effects with less cellular resistance. This follows the introduction of oxaliplatin, water-soluble carboplatin, multinuclear platinum and newly synthesized complexes, etc. Method: This review emphasizes recent advancements in drug design and development, the mechanism of platinum (II) complexes, their stereochemistry, current updates, and biomedical applications of platinum-based anticancer agents. Conclusion: In the last few decades, the popularity of platinum complexes as potent anti-cancer agents has risen as scientists have synthesized many new platinum complexes that exhibit better cytotoxicity coupled with less off-target effects.

scholarly journals Mechanism of RNA polymerase II stalling by DNA alkylation

2017 ◽  
Vol 114 (46) ◽  
pp. 12172-12177 ◽  
Author(s):  
Stefano Malvezzi ◽  
Lucas Farnung ◽  
Claudia M. N. Aloisi ◽  
Todor Angelov ◽  
Patrick Cramer ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Anticancer Agents ◽  
Excision Repair ◽  
Minor Groove ◽  
Dna Alkylation ◽  
Drug Induced ◽  
Rna Pol Ii ◽  
Pol Ii

Several anticancer agents that form DNA adducts in the minor groove interfere with DNA replication and transcription to induce apoptosis. Therapeutic resistance can occur, however, when cells are proficient in the removal of drug-induced damage. Acylfulvenes are a class of experimental anticancer agents with a unique repair profile suggesting their capacity to stall RNA polymerase (Pol) II and trigger transcription-coupled nucleotide excision repair. Here we show how different forms of DNA alkylation impair transcription by RNA Pol II in cells and with the isolated enzyme and unravel a mode of RNA Pol II stalling that is due to alkylation of DNA in the minor groove. We incorporated a model for acylfulvene adducts, the stable 3-deaza-3-methoxynaphtylethyl-adenosine analog (3d-Napht-A), and smaller 3-deaza-adenosine analogs, into DNA oligonucleotides to assess RNA Pol II transcription elongation in vitro. RNA Pol II was strongly blocked by a 3d-Napht-A analog but bypassed smaller analogs. Crystal structure analysis revealed that a DNA base containing 3d-Napht-A can occupy the +1 templating position and impair closing of the trigger loop in the Pol II active center and polymerase translocation into the next template position. These results show how RNA Pol II copes with minor-groove DNA alkylation and establishes a mechanism for drug resistance.

scholarly journals N-Heterocyclic Carbene-PEI Platinum Complexes Inducing Human Cancer Cell Death: Polymer Carrier Impact

2018 ◽  
Author(s):  
May Wantz ◽  
Mathilde Bouche ◽  
Georges Dahm ◽  
Neila Chekkat ◽  
Sylvie Fournel ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Water Solubility ◽  
Human Cancer ◽  
Aqueous Media ◽  
Platinum Complexes ◽  
Polymer Chains ◽  
Polymer Carrier ◽  
Human Cancer Cells ◽  
Cancer Cell Death

The high interest in N-heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. They displayed an effective activity after only 45 minutes of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

scholarly journals Comparative assessment of clinical trials, indications, pharmacokinetic parameters and side effects of approved platinum drugs

Pharmacia ◽  
2022 ◽  
Vol 69 (1) ◽  
pp. 1-7
Author(s):  
Stefka Ivanova
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Observational Study ◽  
Protein Binding ◽  
Anticancer Agents ◽  
Platinum Complexes ◽  
Comparative Assessment ◽  
The Other ◽  
Pharmacokinetic Parameters ◽  
Platinum Drugs

Platinum complexes are among the most commonly applied anticancer agents. The aim of current work is collection, analysing and comparative estimation of clinical trials and pharmacological indications of currently approved for application platinum detivatives: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin (Japan), Lobaplatin (China), Heptaplatin (North Korea), and Satraplatin. The other aim of the study includes the summarizing of the hystoric data for the stages of the developlement of these drugs, and the comparison of pharmacokimetic parameters, side effecs and the dose-liniting factors of the drugs. The observational study on pharmacokinetic parameters shows that protein binding decreases in order: 95% (Cisplatn); 90% (Oxaliplatin); 50% (Nedaplatin); low (Carboplatin). For every of Cisplatin, Carboplatin, Oxaliplatin have been reported more than 1000 clinical trials; for Lobaplatin, Nedaplatin, Satraplatin - about 10 trials. The differenses in dose-limiting effects are: neuro-, nephro-, ototoxicity (Cisplatin); neurotoxicity (Oxaliplatin); nephrotoxicity (Heptaplatin); myelosuppression: thrombocytopenia, neutropenia, leukopenia (Carboplatin, Nedaplatin, Satraplatin).

scholarly journals Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents

2014 ◽  
Vol 1 (3) ◽  
pp. 231-241 ◽  
Author(s):  
Malgorzata Frik ◽  
Josefina Jiménez ◽  
Vadim Vasilevski ◽  
Monica Carreira ◽  
Andreia de Almeida ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Ovarian Cancer Cell ◽  
Platinum Complexes ◽  
Cancer Cell Lines ◽  
Cytotoxic Agents ◽  
Ovarian Cancer Cell Lines ◽  
Palladium And Platinum Complexes

Luminescent d8metals iminophosphorane complexes as potent cytotoxic agents on ovarian cancer cell lines which do not interact with DNA.

scholarly journals Correction: Platinum complexes as light promoted anticancer agents: a redefined strategy for controlled activation

2017 ◽  
Vol 46 (24) ◽  
pp. 7960-7960 ◽  
Author(s):  
Koushambi Mitra
Keyword(s):  
Anticancer Agents ◽  
Platinum Complexes ◽  
Dalton Trans

Correction for ‘Platinum complexes as light promoted anticancer agents: a redefined strategy for controlled activation’ by Koushambi Mitra, et al., Dalton Trans., 2016, 45, 19157–19171.

scholarly journals N-Heterocyclic Carbene-Polyethyleneimine (PEI) Platinum Complexes Inducing Human Cancer Cell Death: Polymer Carrier Impact

2018 ◽  
Vol 19 (11) ◽  
pp. 3472 ◽  
Author(s):  
May Wantz ◽  
Mathilde Bouché ◽  
Georges Dahm ◽  
Neïla Chekkat ◽  
Sylvie Fournel ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Water Solubility ◽  
Human Cancer ◽  
Aqueous Media ◽  
Platinum Complexes ◽  
Polymer Chains ◽  
Polymer Carrier ◽  
Human Cancer Cells ◽  
Cancer Cell Death

The high interest in N-Heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed on 8 different types of cells that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. Using HCT116 cells, the conjugates displayed an effective activity after only 45 min of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

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