It is now 20 years since the publication of the antitumour activity of platinum compounds by barnett rosenberg and his colleagues. Nonplatinum complexes containing releasable biologically active ligands. One of the main disadvantages of cisplatin is that, in many. A copper connection to the uptake of platinum anticancer drugs john l.
Because doublehelical dna has a chiral structure, complexes with enantiomeric ancil. Despite the widespread use of these drugs, the only. Following the unexpected discovery of the anticancer. Multinuclear platinum complexes as anticancer drugs. Toward multitargeted platinum and ruthenium drugsa new. Platinumbased anticancer drugs encapsulated liposome and. Among those affecting patient quality of life are nephrotoxicity, fatigue, emesis, alopecia, ototoxicity, peripheral neuropathy, and. Combining aspects of the platinum anticancer drugs picoplatin and bbr3464 to synthesize a new family of sterically hindered dinuclear complexes. Anticancer drugs the anticancer drug either kill cancer cells or modify their growth. A multifunctional nanobodydrug conjugate ndc was constructed in this work for the targeted delivery of a platinum prodrug and an mri contrast agent. Approximately half of all patients who receive anticancer chemotherapy are treated with a platinum drug. Platinumgroup pg complexes have been used as antibacterial and anticancer agents since the discovery of cisplatin.
Chemistry and molecular biology of platinum anticancer drugs 733 properties of dna fundamental building blocks dna is a polymer composed of a deoxyribose sugarphosphate backbone and four nucleotide bases fig. Cisplatin, carboplatin and oxaliplatin are platinumbased drugs that are widely used in cancer. After removal of the chloride, platinum forms covalent bonds to the n7 of purine bases. Platinum is a chemical element with the symbol pt and atomic number 78. Following these initial successes, liposomal formulations of other agents e.
Pdf the status of platinum anticancer drugs in the. Modular design of nanobodydrug conjugates for targeted. Pdf the status of platinum anticancer drugs in the clinic and in. Platinum is a member of the platinum group of elements and group 10 of the periodic table of elements. Oct 01, 2002 new perspectives for a rational design of platinum antitumor drugs, journal of inorganic biochemistry, 10.
The navigating care library includes articles about cancer, chemotherapy regimens and drugs from the the national cancer institute and other experts. Peptide targeting of platinum anticancer drugs request pdf. Understanding and improving platinum anticancer drugs. Selectivity of terpyridine platinum anticancer drugs for g. Mar 24, 2005 we can anticipate more exciting discoveries in this field in the future, and, with the commitment and backing of the pharmaceutical industry, a new generation of platinum based anticancer drugs. Platinum based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. Platinum anticancer drugs are effective against a wide range of tumors, though their severe adverse effects and resistance remain unresolved. The preferred heavy metal binding sites at neutral ph are n7 of guanine and adenine. Platinum anticancer drugs, chemical biology of chemical. Rodent and nonrodent toxicology studies are currently expected to support phase i trials of antineoplastic drugs in the united states. This agent is curative against most testicular cancers and is highly active against a wide range of other tumor types, notably ovarian, bladder carcinoma, and nonsmallcell lung cancer 1.
Developments in platinum anticancer drugs request pdf. The development of platinum based anticancer compounds has long been focused on the synthesis and evaluation of complexes that obey the sars set forth in the 1970s. To determine the predictive value of these studies, we initiated a project to compare preclinical and clinical toxicity data within various drug classes. Platinum anticancer drugs since cisplatin, the first fda approved ptii anticancer drug, went on the market in 1978, platinum anticancer drugs have been a great success. A platinumbased anticancer drug is any agent that contains one or more platinum atoms in the oxidation state of ii or iv, contains mono or multidentate nonlabile ammine carrier ligands and labile chlorido or bidentate carboxylate ligands, and which acts as a prodrug. Cellular processing of platinum anticancer drugs nature. Pdf combining aspects of the platinum anticancer drugs. Guaninerich dna can form fourstranded structures called gquadruplexes g4s that can regulate many biological processes. Metal complexes have shown high affinity and selectivity toward the quadruplex structure. Request pdf developments in platinum anticancer drugs platinum compounds represent one of the great success stories of metals in medicine. Department of pharmacology and clinical pharmacology, and the auckland cancer society research centre, school of medical sciences, faculty of medical and health sciences. On the other hand, some types of cancer are barely affected by currently.
Chiral discrimination in platinum anticancer drugs michele benedetti, 1 jaroslav malina, 2 jana kasparkova, viktor brabec, 2 and giovanni natile 1 1 dipartimento farmacochimico, universita di bari, bari, italy. Platinumbased anticancer drugs including cisplatin, carboplatin, and oxaliplatin are the most widely used and effective chemotherapeutic agents in the current arsenal 1, 2. No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug. Synthetic strategies for the design of platinum anticancer. After nearly 20 years of research on the use of ruthenium in the fight against cancer, only two ruiii coordination complexes have advanced to clinical trials. Cisplatin cis diamminedichloroplatinum ii is a highly active anticancer agent. Platinum based antineoplastic drugs informally called platins are chemotherapeutic agents used to treat cancer. Here, we report the comparison of a panel of platinum ii complexes for quadruplex dna selective recognition by exploring the aromatic core around. Targeting and delivery of platinumbased anticancer drugs. This agent is curative against most testicular cancers and is.
These pursuits have produced carboplatin and oxaliplatin, two widely employed anticancer drugs. The synthetic chemistry of platinum anticancer agents since the inception of cisplatin as a clinically approved anticancer agent, a large number of platinum compounds have been synthesized with the aim of finding new, improved drugs. They are believed to exert their action by binding to nuclear dna that. Based in part on the article platinumbased anticancer drugs by.
Platinumbased drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of human neoplasms. Polymeric micelles for targeted tumor therapy of platinum. Journal of inorganic biochemistry 2019, 199, 110769. Among those affecting patient quality of life are nephrotoxicity, fatigue, emesis, alopecia, ototoxicity, peripheral neuropathy, and myelosupression 24, 25.
Oct 29, 2002 cisplatin cis diamminedichloroplatinum ii is a highly active anticancer agent. A platinum based anticancer drug is any agent that contains one or more platinum atoms in the oxidation state of ii or iv, contains mono or multidentate nonlabile ammine carrier ligands and labile chlorido or bidentate carboxylate ligands, and which acts as a prodrug. Lippard is the arthur amos noyes professor of chemistry at the massachusetts institute of technology where he was head of the chemistry department from 19952005. The platinum ligand was attached to the peptide via the. The complexes that illustrate the prominent strategies utilized in the development of. Platinum dna adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. Much effort has been put into the development of new platinum anticancer complexes, but none of them has reached worldwide clinical application so far.
The first class analyzed was the platinum anticancer drugs. Membrane transporters as determinants of the pharmacology. Understanding and improving platinum anticancer drugs ncbi. Farrell virginia commonwealth university, richmond, va, usa 9.
Pdf the anticancer power of platinum compounds researchgate. During this time, the field has produced excellent candidate drugs with outstanding in vivo and in vitro activity. Platinum drugs comprise of almost 50% of all currently used anticancer drugs. Chemistry and molecular biology of platinum anticancer drugs. However, the incomplete puzzle of cisplatins ways and the lack of a single decisive biological target for anticancer treatment still complicate the search for improved platinum drugs. Understanding these mechanisms provides important insight for designing more efficient platinum based drugs.
Besides various side effects caused by platinum anticancer drugs, they are not efficiently absorbed by the tumor cells. Understanding and improving platinum anticancer drugs phenanthriplatin. Jan 14, 2019 modulation of ruthenium anticancer drugs analogs with tolfenamic acid. Discovery of anticancer agents started after 1940s when nitrogen mustard was used most of the agents were discovered in 19501970. Anticancer platinum metallodrugs fdaapproved and investigated in clinical trials.
In this form of chemotherapy, popular drugs include cisplatin. The discovery of platinums anticancer properties was made by chance during an experiment in 1965, conducted at michigan state university by barnett rosenberg. This affords primarily 1,2 or 1,3intrastrand crosslinks and a low number of interstrand crosslinks. They are now widely used in the clinical therapy of various solid tumors, including ovarian, head and neck, colorectal. In this form of chemotherapy, popular drugs include cisplatin, oxaliplatin, and carboplatin, but several have been proposed or are under. Anticancer applications and recent investigations of metallodrugs. These drugs are used to treat almost half of people receiving chemotherapy for cancer. Different drug targeting and delivery dtd strategies have been developed t. Platinum based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of human neoplasms. Platinumdna adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. In this form of chemotherapy, popular drugs include cisplatin, oxaliplatin, and carboplatin, but.
Modular design of nanobodydrug conjugates for targeteddelivery of platinum anticancer drugs with an mri contrast agent hai huang, a tiantian wu, a hongdong shi, a yun wu, b hongyi yang, b kai zhong, b yucai wang c and yangzhong liu a. Its name is derived from the spanish term platino, meaning little silver. Chiral discrimination in platinum anticancer drugs. Its name is derived from the spanish term platino, meaning little silver platinum is a member of the platinum group of elements and group 10 of the periodic table of elements. Predictive value of preclinical toxicology studies for. Click the drug name to learn how it works and common side effects. Platinum dna adducts activate several cellular processes that are responsible for the cytotoxicity of the drug. Much effort has been put into the development of new platinum anticancer complexes, but none of them has reached worldwide. New perspectives for a rational design of platinum antitumor drugs, journal of inorganic biochemistry, 10. We can anticipate more exciting discoveries in this field in the future, and, with the commitment and backing of the pharmaceutical industry, a new generation of platinumbased anticancer drugs. He noticed that bacteria ceased to divide when placed in an electric field but what rosenberg also observed was a 300fold increase in the size of the bacteria. Cancer chemotherapy remains an intriguing area of pharmacology.
Platinumbased drugs have become a mainstay of cancer therapy. The science world still requires improvement on these complexes because of multidrug and antineoplastic resistances. He was born in pittsburgh and studied at haverford college b. Targeting of radioactive platinumbisphosphonate anticancer drugs to bone of high metabolic activity scientific reports, apr 2020 robin a. Understanding these mechanisms provides important insight for designing more efficient platinumbased drugs. Reactivity, biological interactions and growth inhibition of yeast cell.
Platinum is usually given in combination with other drugs, commonly vinblastine and bleomycin for testicular cancer. The six platinum anticancer drugs with marketing approval for the treatment of human and animal tumors. Platinumbased antineoplastic drugs informally called platins are chemotherapeutic agents used to treat cancer. Some tumors have a natural or acquired resistance to one class of drugs and, by applying several, it is hoped that an effective reduction in tumor mass can be. The widespread use of platinum agents in the treatment of cancer began with the discovery of the antineoplastic activity of cisplatin by barnett rosenberg in the 1960s. In 1965, rosenberg was looking into the effects of an electric field on the growth of escherichia coli bacteria. The status of platinum anticancer drugs in the clinic and in clinical trials. This combination chemotherapy, as it is known, has several objectives. Modulation of ruthenium anticancer drugs analogs with tolfenamic acid.
On the one hand, use of anticancer drugs produces high rates of cure of diseases, which, without chemotherapy, result in extremely high mortality rates eg, acute lymphocytic leukemia in children, testicular cancer, and hodgkins lymphoma. Pdf the status of platinum anticancer drugs in the clinic. Pappert lecture hall duquesne university stephen j. Twelve platinum analogues that had both preclinical. Usually, these have described the structureactivity relationships which have been established for platinum complexes. This channel is dedicated to students of chemistry, medicine, pharmacy, biology, physics, agriculture and other branches studying chemistry. Cisplatin, carboplatin and oxaliplatin are platinumbased drugs that are widely used in cancer chemotherapy.
However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance. Different drug targeting and delivery dtd strategies have been developed to prevent the shortcomings of platinumbased chemotherapy. Here, we report the comparison of a panel of platinum ii complexes for quadruplex dna selective recognition by exploring the aromatic core around terpyridine derivatives. Increased understanding of the mechanism of the action of cisplatin, as a result of decades of research, is leading to a more rational design of new platinum drugs. This article gives a brief introduction to cisplatin, and subsequently summarizes and evaluates the development of cisplatin derivatives and possible new approaches. Among all this research activity, platinum based antitumor prodrugs that have been photoactivated provide the most important approach to address the problems known to be associated with platinum chemotherapy. Platinumbased anticancer drugs occupy a crucial role in the treatment of various malignant tumours. The ndc can be specifically internalized into egfr positive cancer cells, resulting in higher therapeutic effect and lower sideeffects relative to cisplatin. The clinical use of a photosensitizer in the presence. Despite the clinical success that has been enjoyed by cisplatin, carboplatin, and oxaliplatin, treatment with these compounds inflicts a number of deleterious sideeffects. Treatment failure is frequently caused by the development of resistance to cisplatin. Their clinical success is, however, limited due to severe side effects and intrinsic or acquired resistance to the treatment. It is a dense, malleable, ductile, highly unreactive, precious, silverishwhite transition metal. Platinumbased anti cancer drugs are the backbone of chemotherapy, they play a crucial role in treating various malignant tumor.
To improve the selectivity and efficacy and to mitigate the damaging side effects of cisplatin, photosensitized derivatives, which can only be activated upon light irradiation in cancerous cells, have been introduced as anticancer drugs. They are now widely used in the clinical therapy of various solid tumors, including ovarian, head. Among the 20 platinum complexes which have entered clinical trials, the second compound to be approved in 1989 under the name of paraplatin in usa and france, was the carboplatin. Photoactivated platinumbased anticancer drugs sciencedirect. Polymeric platinumcontaining anticancer drugs johnson. Membrane transporters as determinants of the pharmacology of platinum anticancer drugs volume. The status of platinum anticancer drugs in the clinic and in clinical trials article pdf available in dalton transactions 3935. Jun 06, 2017 this channel is dedicated to students of chemistry, medicine, pharmacy, biology, physics, agriculture and other branches studying chemistry. Pdf multinuclear platinum complexes as anticancer drugs. This composition was selected due to the high antimicrobial effect of silver and for the anticancer properties of platinum. Jude childrens research hospital, 332 north lauderdale, memphis, tn 38105 cisplatin cisdiamminedichloroplatinum ii is a highly active anticancer agent.
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