Platinol
   HOME

TheInfoList



OR:

Cisplatin is a chemotherapy medication used to treat a number of cancers. These include
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an u ...
,
ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
,
cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
,
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
,
bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
,
head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...
,
esophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice ...
,
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
,
mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
,
brain tumors A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondar ...
and
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
. It is given by
injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
. Common side effects include bone marrow suppression,
hearing problems Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken l ...
, including total irreversible hearing loss, usually restricted to one ear,
kidney damage Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...
, and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
. Other serious side effects include numbness, trouble walking, allergic reactions, electrolyte problems, and
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
. Use during pregnancy can cause harm to the developing fetus. Cisplatin is in the
platinum-based antineoplastic Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. ...
family of medications. It works in part by binding to DNA and inhibiting its replication. Cisplatin was discovered in 1845 and licensed for medical use in 1978 and 1979. It is on the World Health Organization's List of Essential Medicines.


Medical use

Cisplatin is administered intravenously as short-term infusion in normal saline for treatment of solid and haematological malignancies. It is used to treat various types of cancers, including
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
s, some
carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
s (e.g., small cell lung cancer,
squamous cell carcinoma of the head and neck Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...
and
ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
),
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
s,
bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
,
cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
, and
germ cell tumor Germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ-cell tumors can be cancerous or benign. Germ cells normally occur inside the gonads (ovary and testis). GCTs that originate outside the gonads may be birth defects resulting from er ...
s. Cisplatin is particularly effective against testicular cancer; its adoption has increased the cure rate from 10% to 85%. A paper published on 17 August 2022 demonstrated that a nanoengineered topical transmucosal cisplatin delivery system can be used as a treatment of oral cancer. PRV111, a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles gives rise to anti-tumor responses in squamous cell tumor. It also reduces cisplatin associated toxicities and prevented tumor recurrence
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
''.'' A high concentration of cytotoxic drugs in the tumor and regional lymph nodes is also retained by PRV111 shown in human studies. Such findings indicate that PRV111 may become a possible treatment of oral cancer in the future. Although further trials are necessary, cisplatin has been studied with Auger therapy to increase the therapeutic effects of cisplatin, without increasing normal tissue toxicities.


Side effects

Cisplatin has a number of side effects that can limit its use: * Nephrotoxicity (kidney damage) is the primary dose-limiting side effect and is of major clinical concern. Cisplatin selectively accumulates into the proximal tubule via basolateral-to-apical transport, where it disrupts mitochondrial energetics and
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
Ca2+ homeostasis and stimulates reactive oxygen species and pro-inflammatory
cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
. Multiple mitigation strategies are being explored clinically and pre-clinically, including hydration regimens,
amifostine Amifostine (ethiofos) is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by Clinigen Group under the trade name Ethyol. Indications Amifostine is used therapeu ...
, transporter inhibitors, antioxidants, anti-inflammatories, and epoxyeicosatrienoic acids and their analogues. * Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment. Common neurological side effects of cisplatin include visual perception and hearing disorder, which can occur soon after treatment begins. While triggering apoptosis through interfering with DNA replication remains the primary mechanism of cisplatin, this has not been found to contribute to neurological side effects. Recent studies have shown that cisplatin noncompetitively inhibits an archetypal, membrane-bound mechanosensitive sodium-hydrogen ion transporter known as NHE-1. It is primarily found on cells of the peripheral nervous system, which are aggregated in large numbers near the ocular and aural stimuli-receiving centers. This noncompetitive interaction has been linked to hydroelectrolytic imbalances and cytoskeleton alterations, both of which have been confirmed in vitro and in vivo. However, NHE-1 inhibition has been found to be both dose-dependent (half-inhibition = 30 μg/mL) and reversible. *
Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
: cisplatin is one of the most emetogenic chemotherapy agents, but this symptom is managed with prophylactic antiemetics ( ondansetron,
granisetron Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the v ...
, etc.) in combination with
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
.
Aprepitant Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and de ...
combined with ondansetron and
dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
has been shown to be better for highly emetogenic chemotherapy than just ondansetron and
dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
. * Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe, although there is ongoing investigation of
acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
injections as a preventative measure. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to
melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
in the stria vascularis of the inner ear or the generation of reactive oxygen species. *
Electrolyte disturbance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the cisplatin. * Hemolytic anemia can be developed after several courses of cisplatin. It is suggested that an antibody reacting with a cisplatin-red-cell membrane is responsible for
hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
. Cisplatin can increase levels of sphingosine-1-phosphate in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, contributing to the development of
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
-related cognitive impairment.


Pharmacology

Cisplatin interferes with DNA replication, which kills the fastest proliferating cells, which in theory are cancerous. Following administration, one chloride ion is slowly displaced by water to give the aquo complex ''cis''- tCl(NH3)2(H2O)sup>+, in a process termed
aquation Aquation is the chemical reaction involving "incorporation of one or more integral molecules of water" with or without displacement of other atoms or groups. The term is typically employed to refer to reactions of metal complexes where an anion is ...
. Dissociation of the chloride is favored inside the cell because the intracellular chloride concentration is only 3–20% of the approximately 100 mM chloride concentration in the extracellular fluid. The water molecule in ''cis''- tCl(NH3)2(H2O)sup>+ is itself easily displaced by the ''N''- heterocyclic bases on DNA.
Guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...
preferentially binds. Subsequent to formation of tCl(guanine-DNA)(NH3)2sup>+, crosslinking can occur via displacement of the other chloride, typically by another guanine. Cisplatin crosslinks DNA in several different ways, interfering with cell division by
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
. The damaged DNA elicits
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
mechanisms, which in turn activate
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
when repair proves impossible. In 2008, researchers were able to show that the apoptosis induced by cisplatin on human colon cancer cells depends on the mitochondrial serine-protease Omi/Htra2. Since this was only demonstrated for colon carcinoma cells, it remains an open question whether the Omi/Htra2 protein participates in the cisplatin-induced apoptosis in carcinomas from other tissues. Most notable among the changes in DNA are the 1,2-intrastrand cross-links with
purine Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
bases. These include 1,2-intrastrand d( GpG) adducts, which form nearly 90% of the adducts, and the less common 1,2-intrastrand d( ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are readily excised by the
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
excision repair (
NER NER may refer to: * New European Recordings, a record label * ISO 3166-1 three letter code for Niger * Named entity recognition, a text processing task that identifies certain words as belonging to one class or another * Northeast Regional, an Amtr ...
). Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly
HMG HMG may refer to: Businesses and organisations * His Majesty's Government (term), a Commonwealth state's executive **Government of Canada **Government of Gibraltar **Government of New Zealand **Government of the United Kingdom * Holland Media Groe ...
domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action.


Cisplatin resistance

Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum responsiveness is high, but the majority of cancer patients will eventually relapse with cisplatin-resistant disease. Many mechanisms of cisplatin resistance have been proposed, including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and increased
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
.
Oxaliplatin Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by injection into a vein. Common side effects include numbness, feeling ti ...
is active in highly cisplatin-resistant cancer cells in the laboratory; however, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer. The drug
paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
may be useful in the treatment of cisplatin-resistant cancer; the mechanism for this activity is as yet unknown.


Transplatin

Transplatin ''trans''-Dichlorodiammineplatinum(II) is the trans isomer of the coordination complex with the formula ''trans''-PtCl2(NH3)2, sometimes called ''transplatin''. It is a yellow solid with low solubility in water but good solubility in DMF. The ex ...
, the ''trans''-stereoisomer of cisplatin, has formula ''trans''- tCl2(NH3)2and does not exhibit a comparably useful pharmacological effect. Two mechanisms have been suggested to explain the reduced anticancer effect of transplatin. Firstly, the ''trans'' arrangement of the chloro ligands is thought to confer transplatin with greater chemical reactivity, causing transplatin to become deactivated before it reaches the DNA, where cisplatin exerts its pharmacological action. Secondly, the stereo-conformation of transplatin is such that it is unable to form the characteristic 1,2-intrastrand d(GpG) adducts formed by cisplatin in abundance.


Molecular structure

Cisplatin is the
square planar The square planar molecular geometry in chemistry describes the stereochemistry (spatial arrangement of atoms) that is adopted by certain chemical compounds. As the name suggests, molecules of this geometry have their atoms positioned at the corne ...
coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
cis- t(NH3)2Cl2 The prefix ''cis'' indicates the ''cis'' isomer in which two similar ligands are in adjacent positions. The systematic chemical name of this molecule is ''cis''–diamminedichloroplatinum, where ''ammine'' with two m's indicates an
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...
(NH3)
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
, as opposed to an organic
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
with one m.


History

The compound ''cis''- t(NH3)2Cl2was first described by Italian chemist
Michele Peyrone Michele (), is an Italian male given name, akin to the English male name Michael. Michele (pronounced ), is also an English female given name that is derived from the French Michèle. It is a variant spelling of the more common (and identically ...
in 1845, and known for a long time as Peyrone's salt. The structure was deduced by
Alfred Werner Alfred Werner (12 December 1866 – 15 November 1919) was a Swiss chemist who was a student at ETH Zurich and a professor at the University of Zurich. He won the Nobel Prize in Chemistry in 1913 for proposing the octahedral configuration of ...
in 1893. In 1965,
Barnett Rosenberg Barnett Rosenberg (16 November 1926 – 8 August 2009) was an American chemist best known for the discovery of the anti-cancer drug cisplatin. Rosenberg graduated from Brooklyn College in 1948 and obtained his PhD in physics at New York Universi ...
, Van Camp et al. of
Michigan State University Michigan State University (Michigan State, MSU) is a public university, public Land-grant university, land-grant research university in East Lansing, Michigan. It was founded in 1855 as the Agricultural College of the State of Michigan, the fi ...
discovered that
electrolysis In chemistry and manufacturing, electrolysis is a technique that uses direct electric current (DC) to drive an otherwise non-spontaneous chemical reaction. Electrolysis is commercially important as a stage in the separation of elements from n ...
of platinum electrodes generated a soluble platinum complex which inhibited binary fission in ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' (''E. coli'') bacteria. Although bacterial cell growth continued, cell division was arrested, the bacteria growing as filaments up to 300 times their normal length. The octahedral Pt(IV) complex ''cis''- tCl4(NH3)2 but not the ''trans'' isomer, was found to be effective at forcing filamentous growth of ''E. coli'' cells. The square planar Pt(II) complex, ''cis''- tCl2(NH3)2turned out to be even more effective at forcing filamentous growth. This finding led to the observation that ''cis''- tCl2(NH3)2was indeed highly effective at regressing the mass of
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
s in
rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...
s. Confirmation of this discovery, and extension of testing to other tumour cell lines launched the medicinal applications of cisplatin. Cisplatin was approved for use in testicular and ovarian cancers by the U.S. Food and Drug Administration on 19 December 1978. and in the UK (and in several other European countries) in 1979. Cisplatin was the first to be developed. In 1983 pediatric oncologist Roger Packer began incorporating cisplatin into adjuvant chemotherapy for the treatment of childhood medulloblastoma. The new protocol that he developed led to a marked increase in disease-free survival rates for patients with medulloblastoma, up to around 85%. The Packer Protocol has since become a standard treatment for medulloblastoma. Likewise, cisplatin has been found to be particularly effective against
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an u ...
, where its use improved the cure rate from 10% to 85%. Recently, some researchers have investigated at the preclinical level new forms of cisplatin
prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
s in combination with
nanomaterials * Nanomaterials describe, in principle, materials of which a single unit is sized (in at least one dimension) between 1 and 100 nm (the usual definition of nanoscale). Nanomaterials research takes a materials science-based approach to nan ...
in order to localize the release of the
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
in the target.


Synthesis

Syntheses of cisplatin start from
potassium tetrachloroplatinate Potassium tetrachloroplatinate(II) is the chemical compound with the formula K2PtCl4. This reddish orange salt is an important reagent for the preparation of other coordination complexes of platinum. It consists of potassium cations and the squar ...
. Several procedures are available. One obstacle is the facile formation of
Magnus's green salt Magnus's green salt is the inorganic compound with the formula t(NH3)4PtCl4]. This salt is named after Heinrich Gustav Magnus, who, in the early 1830s, first reported the compound. The compound is a linear chain compound, consisting of a chain of ...
(MGS), which has the same empirical formula as cisplatin. The traditional way to avoid MGS involves the conversion of K2PtCl4 to K2PtI4, as originally described by Dhara. Reaction with
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...
forms PtI2(NH3)2 which is isolated as a yellow compound. When
silver nitrate Silver nitrate is an inorganic compound with chemical formula . It is a versatile precursor to many other silver compounds, such as those used in photography. It is far less sensitive to light than the halides. It was once called ''lunar caustic' ...
in water is added insoluble
silver iodide Silver iodide is an inorganic compound with the formula Ag I. The compound is a bright yellow solid, but samples almost always contain impurities of metallic silver that give a gray coloration. The silver contamination arises because AgI is hig ...
precipitates and t(OH2)2(NH3)2NO3)2 remains in solution. Addition of
potassium chloride Potassium chloride (KCl, or potassium salt) is a metal halide salt composed of potassium and chlorine. It is odorless and has a white or colorless vitreous crystal appearance. The solid dissolves readily in water, and its solutions have a salt ...
will form the final product which precipitates In the triiodo intermediate the addition of the second ammonia ligand is governed by the
trans effect In inorganic chemistry, the trans effect is the increased lability of ligands that are trans to certain other ligands, which can thus be regarded as trans-directing ligands. It is attributed to electronic effects and it is most notable in square pl ...
. : A
one-pot synthesis In chemistry a one-pot synthesis is a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one reactor. This is much desired by chemists because avoiding a lengthy separ ...
of cisplatin from K2PtCl4 has been developed. It relies on the slow release of ammonia from ammonium acetate.


See also

*
Carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...
* Dicycloplatin


References


Further reading

*


External links

*
IARC Monograph: "Cisplatin"
{{portal bar, Medicine Ammine complexes Bioinorganic chemistry Cancer treatments Chloro complexes Coordination complexes IARC Group 2A carcinogens Medicinal inorganic chemistry Metal-containing drugs Nephrotoxins Platinum complexes Platinum-based antineoplastic agents Platinum(II) compounds World Health Organization essential medicines Wikipedia medicine articles ready to translate