scholarly journals Cell-Permeable Lanthanide-Platinum(IV) Anti-Cancer Prodrugs

2021 ◽  
Author(s):  
Kezi Yao ◽  
Gogulan Karunanithy ◽  
Alison Howarth ◽  
Phil Holdship ◽  
Amber L Thompson ◽  
...  

Platinum compounds are a vital part of our anti-cancer arsenal, determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group...

Author(s):  
Rajiv Sharma ◽  
Vikram Jeet Singh ◽  
Pooja A Chawla

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.


Symmetry ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 749
Author(s):  
Beata Szefler ◽  
Przemysław Czeleń

Platinum compounds are anti-cancer drugs and can bind to canonical purine bases, mainly guanine, found within double helical DNA. Platinum compounds can be transferred directly to pathologically altered sites in a specific and site-oriented manner by nanocarriers as potential nanocarriers for carboplatin. Two types of nanostructures were used as potential nanocarriers for carboplatin, the first were functionalized C60 fullerene molecules and the second were rhombellanes. The analyzed nanostructures show considerable symmetry, which affects the affinity of the studied nanocarriers and ligands. Thus symmetry of nanostructures affects the distribution of binding groups on their surface. After the docking procedure, analysis of structural properties revealed many interesting features. In all described cases, binding affinities of complexes of platinum compounds with functionalized fullerene C60 are higher compared with affinities of complexes of platinum compounds with rhombellane structures. All platinum compounds easily create complexes with functionalized fullerene C60, CID_16156307, and at the same time show the highest binding affinity. The binding affinities of lobaplatin and heptaplatin are higher compared with oxaliplatin and nedaplatin. The high value of binding affinity and equilibrium constant K is correlated with creation of strong and medium hydrogen bonds or is correlated with forming a hydrogen bond network. The performed investigations enabled finding nanocarriers for lobaplatin, heptaplatin, oxaliplatin and nedaplatin molecules.


Author(s):  
S. K. Aggarwal ◽  
P. McAllister ◽  
R. W. Wagner ◽  
B. Rosenberg

Uranyl acetate has been used as an electron stain for en bloc staining as well as for staining ultrathin sections in conjunction with various lead stains (Fig. 1). Present studies reveal that various platinum compounds also show promise as electron stains. Certain platinum compounds have been shown to be effective anti-tumor agents. Of particular interest are the compounds with either uracil or thymine as one of the ligands (cis-Pt(II)-uracil; cis-Pt(II)-thymine). These compounds are amorphous, highly soluble in water and often exhibit an intense blue coloration. These compounds show enough electron density to be used as stains for electron microscopy. Most of the studies are based on various cell lines (human AV, cells, human lymphoma cells, KB cells, Sarcoma-180 ascites cells, chick fibroblasts and HeLa cells) while studies on tissue blocks are in progress.


2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.


Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki

2010 ◽  
Author(s):  
N. Magnavita ◽  
I. lavicoli ◽  
V. Leso ◽  
A. Bergamaschi

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
S Thamburan ◽  
F February ◽  
M Meyer ◽  
J Rees ◽  
Q Johnson
Keyword(s):  

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