125074-46-6

Basic information

• Product Name: {Pt(2)(OH)2}
• CAS NO: 125074-46-6
• Molecular Weight: 334.062
• Mol File: 125074-46-6.mol
• Article Data: 67

Chemical Properties

• CAS DataBase Reference: {Pt(2)(OH)2}(CAS DataBase Reference)
• NIST Chemistry Reference: {Pt(2)(OH)2}(125074-46-6)
• EPA Substance Registry System: {Pt(2)(OH)2}(125074-46-6)

Safety Data

• Hazardous Substances Data: 125074-46-6(Hazardous Substances Data)

Upstream product

• 26035-31-4 cisplatine 
• 7722-84-1 dihydrogen peroxide 
• 15663-27-1 cisplatin 
• 7732-18-5 water 
• 26035-31-4 transplatin 
• 7722-64-7 potassium permanganate 

Downstream Products

• 16893-05-3 cis-diaammineplatinum(IV) tetrachloride 
• 15663-27-1 cisplatin 
• 1613703-75-5 C₃₈H₃₆Cl₄N₄O₈Pt 

Relevant articles and documents

Chlorambucil-conjugated platinum(IV) prodrugs to treat triple-negative breast cancer in vitro and in vivo

Modification of platinum (II) into lipophilic platinum (IV) compounds by introducing biologically active molecules were widely employed to develop new platinum-based prodrugs in the past decade. In this paper, two chlorambucil platinum (IV) complexes, CLB-Pt and CLB-Pt-CLB, were synthesized and displayed very potent antiproliferative activity against all the tested cancer cell lines, such as A549, HeLa and MCF-7, especially to treat the well-known refractory triple-negative breast cancer. CLB-Pt-CLB significantly improved cell-killing effect in triple-negative subtype MDA-MB-231 cells, and showed much stronger cytotoxicity than either monotherapy or combination of cisplatin and chlorambucil. CLB-Pt-CLB prodrug entered cells in dramatically increased amount compared with cisplatin and enhanced DNA damage, inducing cancer cell apoptosis. It exhibited high anticancer activity and no observable toxicity in BALB/c nude mice bearing MDA-MB-231 tumors. The chlorambucil moiety not only greatly assisted the passive diffusion of CLB-Pt-CLB into cells, but also produced the synergism with cisplatin in targeting DNA.

Synthesis and characterization of hyaluronic acid-platinum(IV) nanoconjugate with enhanced antitumor response and reduced adverse effects

A hyaluronic acid-platinum(iv) nanoconjugate with a high drug loading capacity was developed to mitigate the side effects of platinum(ii). Pt(iv), HA-EDA, and HA-EDA-Pt(iv) nanoconjugates were investigated by 1H NMR, 13C NMR, FT-NIR, and DSC. Negatively charged polymer-drug conjugates were of a uniform size around 186.4 nm and spherical in shape. In vitro antiproliferation and in vivo apoptosis assays proved that the nanomedicine possessed high cytotoxicity towards cancer cells. The enhanced antitumor effect was attributed to HA receptor-mediated endocytosis. Nanoscale conjugates exhibited desirable blood compatibility and negligible stimulation to blood vessels. The systemic toxicity study showed that polymer-drug conjugates were much safer than the parent drug evidenced by biochemical and histological analyses. The concise design of the nanoconjugate offers a simple way to overcome the toxicity and non-selectivity of cisplatin, which could improve therapeutical outcomes of platinum drugs in cancer therapy.

The dual-role of Pt(iv) complexes as active drug and crosslinker for micelles based on β-cyclodextrin grafted polymer

With a combination of RAFT and click chemistry an amphiphilic block copolymer with poly(ethylene glycol) methyl ether methacrylate (POEGMEMA) as hydrophilic block and poly(propargyl methacrylate) (PMA) as hydrophobic block has been successfully synthesized. To this, 6-azide-6-deoxy-β-cyclodextrin (N3-β-CD) was clicked creating a hosting environment for a hydrophobic small molecule platinum pro-drug. Oxoplatin, the oxidized version of cisplatin, has been modified on its axial ligand introducing cholic acid groups through esterification. This modified cisplatin forms a host-guest complex with β-cyclodextrin that has been characterised via NMR spectroscopy. The host-guest interaction that the drug established with the β-cyclodextrin grafted copolymer drove the self-assembly into nanoparticles of a diameter of 266 nm able to physical encapsulate the platinum-based drug. In the presence of ascorbic acid, 70% of the pro-drug is released over a period of 24 h. Cytotoxicity assays on ovarian cancer cells show that the polymer carrier improves the cytotoxicity of the platinum pro-drug. The IC50 value decreases from 37.7 μM with the pro-drug to 20.4 μM when the pro-drug is encapsulated into the polymer carrier. This is due to the fact that the uptake of the polymer carrier is up to 6 fold higher than the significantly smaller pro-drug by itself.

DNA Nanostructures as Pt(IV) Prodrug Delivery Systems to Combat Chemoresistance

Cisplatin is a first-line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these DNA nanostructures could remarkably enhance the cellular internalization of platinum drugs and thus increase the anticancer activity, not only to regular lung cancer cells (A549), but more importantly to cisplatin-resistant cancer cells (A549cisR). Further, in vivo studies also demonstrate that cisplatin prodrug loaded DNA nanostructures could effectively suppress tumor growth in both regular and cisplatin-resistant tumor models. This study suggests that DNA nanostructures are effective carriers for platinum prodrug delivery to combat chemoresistance.

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX-2 and PD-L1

Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase-2 (COX-2) plays a vital role in the progression of BC, correlating with the expression of programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple-negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule.

Lung cancer combination treatment: Evaluation of the synergistic effect of cisplatin prodrug, vinorelbine and retinoic acid when co-encapsulated in a multi-layered nano-platform

Purpose: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CIS) was often used in combination with other drugs for the treatment of non-small cell lung cancer (NSCLC). Prodrug is an effective strategy to improve the efficiency of drugs and reduce the toxicity. The aim of this study was to prepare and characterize CIS prodrug, vinorelbine (VNR), and all-trans retinoic acid (ATRA) co-delivered multi-layered nano-platform, evaluating their antitumor activity in vitro and in vivo. Methods: Cisplatin prodrug (CISP) was synthesized. A multi-layered nano-platform contained CISP, VNR and ATRA were prepared and named CISP/VNR/ATRA MLNP. The physicochemical properties of CISP/VNR/ATRA MLNP were investigated. In vitro cytotoxicity against CIS-resistant NSCLC cells (A549/CIS cells) and Human normal lung epithelial cells (BEAS-2B cells) was investigated, and in vivo anti-tumor efficiency was evaluated on mice bearing A549/CIS cells xenografts. Results: CISP/VNR/ATRA MLNP were spherical particles with particle size and zeta potential of 158 nm and 12.3 mV. CISP/VNR/ATRA MLNP (81.36%) was uptake by cancer cells in vitro. CISP/VNR/ATRA MLNP could significantly inhibit the in vivo antitumor growth and suspended the tumor volume from 1440 mm3 to 220 mm3. Conclusion: It could be concluded that the CISP/VNR/ATRA MLNP may be used as a promising system for lung cancer combination treatment.

New NSAID-Pt(IV) prodrugs to suppress metastasis and invasion of tumor cells and enhance anti-tumor effect in vitro and in vivo

The great interest in epithelial-to-mesenchymal transition (EMT) programme lies in its association with process of metastasis and invasion, which is a crucial cause of cancer-related death. Herein, we designed and reported three new NSAID-Pt(IV) prodrugs, taking Non-Steroid Anti-Inflammatory Drugs (NSAIDs) to disrupt EMT programme and assist genotoxic platinum-based drugs as a cytotoxicity booster, to offer a class of potential anticarcinogens with a multi-functional action mechanism. The NSAID-Pt(IV) prodrugs, especially Eto-Pt(IV), highly enhanced cellular uptake with amount up to 42-fold at 3 h compared with CDDP, and greatly increased DNA damage and cell apoptosis, showing much higher cytotoxicity than cisplatin in the tested cancer cells even in A549/cis cells. Among of them, Eto-Pt(IV) and Car-Pt(IV) exhibited more excellent activity than Sul-Pt(IV), arising from their reduction-labile and favorable lipophilicity. Most strikingly, Eto-Pt(IV) markedly inhibited metastasis and invasion of MCF-7 cells, owing to its COX-2 suppression that down-regulated active MMP-2, vimentin protein and up-regulated E-cadherin. In vivo, Eto-Pt(IV) displayed potent antitumor activity and no observable toxicity in BALB/c nude mice bearing MCF-7 tumors.

Immobilization of Platinum(II) and Platinum(IV) Complexes on Oxidized Nanoporous Carbon Material and Evaluation of the Enthalpy of Adsorption

Physicochemical study of cis-[Pt(NH3)2Cl2] and cis-[Pt(NH3)2Cl2(OH)2] is carried out, and immobilization of platinum complexes on the nanoporous carbon substrate is investigated. The solubility of cis-[Pt(NH3)2Cl2] in 1 M HCl solution is determined, and the average enthalpy of dissolution is calculated: ΔsolH° = 27.3 ± 0.9 kJ/mol. The batch capacity is determined experimentally for cis-[Pt(NH3)2Cl2] and cis- [Pt(NH3)2Cl2(OH)2] to be 32.9 mg/g (0.17 mg-equiv/g) and 47.6 mg/g (0.24 mg-equiv/g), respectively. Immobilization of platinum complexes on the oxidized carbon surface is found to take place due to interaction between carboxy groups and ammine groups of platinum complexes. The resulting heat capacity curves are used to calculate the enthalpies of adsorption for cis-[Pt(NH3)2Cl2] and cis-[Pt(NH3)2Cl2(OH)2] on the oxidized carbon surface, equal to 24.46 and 27.46 kJ/mol, respectively.

Cisplatin-modified isonicotinic acid as a?potential linker in bio-MOFs: synthesis and characterization

Abstract: The platinum derivative cisplatin is widely used against many types of cancers effectively. However, cisplatin has limitations such as toxicity, resistances, and being thermally labile, non-volatile, and highly insoluble. To overcome these limitations, cisplatin with platinum(II) as metal centers needs to be modified to platinum(IV). Modification of platinum(IV) of cisplatin ligated to an organic ligand in the axial position could be a strategy to reduce its toxicity and increase the lifetime in blood when administered as an oral prodrug as an anti-cancer agent. The complex also has potential to be employed as a linker in bio-metal–organic frameworks (bioMOFs) synthesis and has good stability. Cisplatin-modified ligand also has a large size which can affect to the pore size on bioMOFs. Isonicotinic acid is a pyridine derivative with pyridine and carboxyl as an active group that can make coordination with metal ions on bioMOF assemblies. In this study, a simple and efficient method for the synthesis of a novel cisplatin-modified isonicotinic acid, nicoplatin, was reported. A substitution reaction possibly occurs on the axial position of oxoplatin by isonicotinic acid ligand. The obtained compound was fully characterized with FTIR, 1H-NMR, 13C-NMR, ESI–MS and elemental analyses. Graphical abstract: [Figure not available: see fulltext.].

BODI-Pt, a Green-Light-Activatable and Carboplatin-Based Platinum(IV) Anticancer Prodrug with Enhanced Activation and Cytotoxicity

Platinum drugs are widely used in clinics to treat various types of cancer. However, a number of severe side effects induced by the nonspecific binding of platinum drugs to normal tissues limit their clinical use. The conversion of platinum(II) drugs into more inert platinum(IV) derivatives is a promising strategy to solve this problem. Some platinum(IV) prodrugs, such as carboplatin-based tetracarboxylatoplatinum(IV) prodrugs, are not easily reduced to active platinum(II) species, leading to low cytotoxicity in vitro. In this study, we report the design and synthesis of a carboplatin-based platinum(IV) prodrug functionalized with a boron dipyrromethene (bodipy) ligand at the axial position, and the ligand acts as a photoabsorber to photoactivate the platinum(IV) prodrug. This compound, designated as BODI-Pt, is highly stable in the dark but quickly activated under irradiation to release carboplatin and the axial ligands. A cytotoxic study reveals that BODI-Pt is effective under irradiation, with cytotoxicity 11 times higher than that in the dark and 39 times higher than that of carboplatin in MCF-7 cells. Moreover, BODI-Pt has been proven to kill cancer cells by binding to the genomic DNA, arresting the cell cycle at the G2/M phase, inducing oncosis, and generating ROS upon irradiation. In summary, we report a green-light-activatable and carboplatin-based Pt(IV) prodrug with improved cytotoxicity against cancer cells, and our strategy can be used as a promising way to effectively activate carboplatin-based platinum(IV) prodrugs.

A Nanoparticle Cocktail: Temporal Release of Predefined Drug Combinations

A single magic bullet is not enough for treatment of metastatic cancers. However, administration of a combination of free drugs can be extremely challenging because of the inability to control the correct choice of dosages and definitive delivery of the effective drug ratio at the target tissue due to the differences in pharmacokinetics and biodistribution of individual drugs. Here we report an engineered biodegradable polymer containing combination therapeutics that can be self-assembled into a controlled release nanoparticle with abilities to deliver multiple therapeutics in a predefined ratio following temporal release patterns. This platform technology can lead to a rationally designed combination therapy.

Targeting Energy Metabolism by a Platinum(IV) Prodrug as an Alternative Pathway for Cancer Suppression

Cancer is characterized by abnormal cellular energy metabolism, which preferentially switches to aerobic glycolysis rather than oxidative phosphorylation as a means of glucose metabolism. Many key enzymes involved in the abnormal glycolysis are potential targets of anticancer drugs. Platinum(IV) complexes are potential anticancer prodrugs and kinetically more inert than the platinum(II) counterparts, which offer an opportunity to be modified by functional ligands for activation or targeted delivery. A novel platinum(IV) complex, c,c,t-[Pt(NH3)2Cl2(C10H15N2O3S)(C2HO2Cl2)] (DPB), was designed to explore the effects of axial ligands on the reactivity and bioactivity of the complex as well as on tumor energy metabolism. The complex was characterized by electrospray ionization mass spectrometry and multinuclear (1H, 13C, and 195Pt) NMR spectroscopy. The introduction of dichloroacetate (DCA) markedly increases the lipophilicity, reactivity, and cytotoxicity of the complex and blocks the growth of cancer cells having active glycolysis, and the introduction of biotin (C10H16N2O3S) enhances the tumor-targeting potential of the complex. The cytotoxicity of DPB is increased dramatically in a variety of cancer cell lines as compared with the platinum(IV) complex PB without the DCA group. DPB alters the mitochondrial membrane potential and disrupts the mitochondrial morphology. The levels of mitochondrial and cellular reactive oxygen species are also decreased. Furthermore, the mitochondrial function of tumor cells was impaired by DPB, leading to the inhibition of both glycolysis and glucose oxidation and finally to the death of cancer cells via a mitochondria-mediated apoptotic pathway. These findings demonstrate that DPB suppresses cancer cells mainly through altering metabolic pathways and highlight the importance of dual-targeting for the efficacy of anticancer drugs.

Tetravalent veratric acid platinum as well as preparation method and application thereof

The invention belongs to the technical field of medicine, and particularly relates to tetravalent veratric acid platinum as well as a preparation method and application thereof, the structural formula of the tetravalent veratric acid platinum is shown in the specification, and the preparation method comprises the following steps: (1) synthesizing hydroxyl platinum; (2) synthesizing tetravalent platinum veratryl acid; and (3) purifying tetravalent platinum veratryl acid. The tetravalent veratric acid platinum provided by the invention belongs to a tetravalent platinum prodrug, is a novel efficient anti-tumor active compound, has a broad-spectrum anti-cancer effect, is small in killing effect on normal cells of a human body, is efficient and low in toxicity, has a relatively high medicinal value, and is simple in preparation method, low in cost and easy for industrial production.

Photothermal Therapy via NIR II Light Irradiation Enhances DNA Damage and Endoplasmic Reticulum Stress for Efficient Chemotherapy

Ovarian cancer has the highest death rate in gynecologic tumors and the main therapy for patients with advanced is chemotherapy based on cisplatin. Additionally, hyperthermic intraperitoneal has been used in clinic to obtain better efficacy for patients. Hence, combined photothermal therapy with platinum drugs in a new delivery system might bring new hope for ovarian cancer. A reduction sensitive polymer encapsulating a Pt (IV) prodrug and a near infrared II (NIR II) photothermal agent IR1048 to form nanoparticles were reported to enhance the efficacy of ovarian cancer treatment. At the same time, endoplasmic reticulum stress indicates an imbalance in proteostasis which probably caused by extrinsic stress such as chemotherapy and the temperature changed. The efficacy of nanoparticles containing Pt (IV) and IR1048 under NIR II light might be caused via increased DNA damage and endoplasmic reticulum (ER) stress.