Metal-Based Drugs最新文献

{"title":"Synthesis and anchoring of antineoplastic ferrocene and phthalocyanine derivatives on water-soluble polymeric drug carriers derived from lysine and aspartic Acid.","authors":"M David Maree,&nbsp;Eberhard W Neuse,&nbsp;Elizabeth Erasmus,&nbsp;Jannie C Swarts","doi":"10.1155/2008/217573","DOIUrl":"https://doi.org/10.1155/2008/217573","url":null,"abstract":"<p><p>The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N('),N(')-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"217573"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/217573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-containing proteins, macrocycles, and coordination complexes in therapeutic applications and disease.","authors":"Jannie C Swarts,&nbsp;Michael J Cook,&nbsp;Edward N Baker","doi":"10.1155/2008/286363","DOIUrl":"https://doi.org/10.1155/2008/286363","url":null,"abstract":"Treatment of diseases with natural and synthetic materials has been an aspiration of mankind since the dawn of human development. From the use of willow-bark to the marketing of aspirin, a steady move from folk remedies to the use of chemistry and biology to develop new therapies has been observed. In terms of metal-containing drugs, the platinum-containing drug cisplatin has long been the most effective metal-containing anticancer drug on the market. \u0000 \u0000However, severe side effects of conventional drugs are associated with the inability to distinguish between healthy and cancer cells. Hence, a concerted world-wide effort is in progress to discover and characterise new drugs that may distinguish between healthy and cancer or other diseased cells. New techniques of drug delivery are sought and the use of natural products, proteins, antibodies, and synthetic polymers as drug delivery devices capable of targeting a diseased site is being investigated. \u0000 \u0000These issues are nicely illustrated by macrocycles such as porphyrins, phthalocyanines, and related systems. Some of these compounds exhibit selective absorption by cancer cells and have the ability to photosensitize formation of singlet oxygen. These attributes have led to the development of alternative cancer treatments known as photodynamic therapy. Sadly, many potentially good new therapeutic agents often never leave the designers' laboratory due to some pharmacological problems associated with its in vivo use. The use of drug delivering devices, including water-soluble synthetic polymeric drug delivery systems, may help overcome many pharmacological drug-related problems, including those of solubility, specificity, and biocompatibility, factors that currently prevent many potentially good therapeutic agents from reaching clinics. \u0000 \u0000The focus of this special issue is the synthesis, characterisation, physical studies, and application of synthetic metal-containing complexes and natural occurring proteins in serious human diseases such as cancer, diabetes, arthritis, viral disease, malaria, and tuberculosis with special focus on the following: \u0000 \u0000 \u0000 \u0000 \u0000 \u0000porphyrins, phthalocyanines, and related complexes in photodynamic cancer therapy; \u0000 \u0000 \u0000proteins, enzymes, and synthetic polymeric drug delivery systems in the treatment of cancer and other diseases; \u0000 \u0000 \u0000coordination and organometallic compounds in cancer, arthritis, malaria, and viral disease. \u0000 \u0000 \u0000 \u0000 \u0000 \u0000 \u0000Towards these goals, L. Josefsen and R. Boyle describe in their review article the development and application of metal-based photosensitisers, including porphyrins and phthalocyanines, in photodynamic therapy. Four other publications highlight different aspects of porphyrin-based macrocyclic photosensitisers. S. Lee et al. focus on the cellular uptake and toxicity of thiotetra (ethylene glycol) monomethyl ether-functionalized porphyrazines. J.-Y. Liu et al. focus on in vitro photodynamic activity of novel amphiphilic zinc(II) phthalocyanines ","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":" ","pages":"286363"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/286363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27690966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metallocene antimalarials: the continuing quest.","authors":"Margaret A L Blackie,&nbsp;Kelly Chibale","doi":"10.1155/2008/495123","DOIUrl":"https://doi.org/10.1155/2008/495123","url":null,"abstract":"<p><p>Over the last decade, a significant body of research has been developed around the inclusion of a metallocene moiety into known antimalarial compounds. Ferroquine is the most successful of these compounds. Herein, we describe our contribution to metallocene antimalarials. Our approach has sought to introduce diversity sites in the side chain of ferroquine in order to develop a series of ferroquine derivatives. The replacement of the ferrocenyl moiety with ruthenocene has given rise to ruthenoquine and a modest series of analogues. The reaction of ferroquine and selected analogues with Au(PPh3)NO3, Au(C6F5)(tht), and [Rh(COD)Cl2] has resulted in a series of heterobimetallic derivatives. In all cases, compounds have been evaluated for in vitro antiplasmodial activity in both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Preliminary structure-activity relationships have been delineated.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":" ","pages":"495123"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/495123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27264993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic approaches in understanding action mechanisms of metal-based anticancer drugs.","authors":"Ying Wang,&nbsp;Jen-Fu Chiu","doi":"10.1155/2008/716329","DOIUrl":"https://doi.org/10.1155/2008/716329","url":null,"abstract":"<p><p>Medicinal inorganic chemistry has been stimulating largely by the success of the anticancer drug, cisplatin. Various metal complexes are currently used as therapeutic agents (e.g., Pt, Au, and Ru) in the treatment of malignant diseases, including several types of cancers. Understanding the mechanism of action of these metal-based drugs is for the design of more effective drugs. Proteomic approaches combined with other biochemical methods can provide comprehensive understanding of responses that are involved in metal-based anticancer drugs-induced cell death, including insights into cytotoxic effects of metal-based anticancer drugs, correlation of protein alterations to drug targets, and prediction of drug resistance and toxicity. This information, when coupled with clinical data, can provide rational basses for the future design and modification of present used metal-based anticancer drugs.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"716329"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/716329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Spectroscopic, and Anticancerous Properties of Mixed Ligand Palladium(II) and Silver(I) Complexes with 4,6-Diamino-5-hydroxy-2-mercaptopyrimidine and 2,2'-Bipyridyl.","authors":"Sahar I Mostafa, Farid A Badria","doi":"10.1155/2008/723634","DOIUrl":"10.1155/2008/723634","url":null,"abstract":"<p><p>Synthesis of two new water-soluble mixed ligand [Pd(bpy)(dahmp)]Cl and [Ag(bpy)(Hdahmp)]NO(3) complexes (dahmp and Hdahmp are the deprotonated monoanion and the protonated neutral 4,6-diamino-5-hydroxy-2-mercaptopyrimidine, resp.) is reported. The composition of the reported complexes was discussed on the bases of IR, (1)H NMR, and mass spectra, as well as conductivity and thermal measurements. The reported complexes display a significant anticancer activity against Ehrlich ascites tumor cells (EACs). The higher activity of these complexes with their higher conductivity values corresponds to their complete ionization in aqueous solution.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"723634"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9367108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Zinc bis(1,4-didecylbenzo)-bis(2,3-pyrido) Porphyrazine for Application as Photosensitizer in Photodynamic Therapy of Cancer.","authors":"Keiichi Sakamoto,&nbsp;Eiko Ohno-Okumura,&nbsp;Taku Kato,&nbsp;Masaki Watanabe,&nbsp;Michael J Cook","doi":"10.1155/2008/392090","DOIUrl":"https://doi.org/10.1155/2008/392090","url":null,"abstract":"<p><p>The phthalocyanine analogue containing nonperipheral long alkyl-substituted benzenoid rings and pyridine rings, zinc bis(1,4-didecylbenzo)-bis(2,3-pyrido) porphyrazine, was synthesized. Zinc bis(1,4-didecylbenzo)-bis(2,3-pyrido) porphyrazine reacted with dimethyl sulfate and monochloroacetic acid to produce their quaternized products and diethyl sulfate to produce the sulfo-substituted products. All quaternized and sulfo-substituted showed amphiphilic character. Identical peaks in cyclic voltammograms appeared for these products before and after quaternization. During the evaluation of zinc bis(1,4-didecylbenzo)-bis(2,3-pyrido) porphyrazine for its photodynamic therapy of cancer (PDT) efficacy by cancer cell culture, the light exposed dimethyl sulfate quaternized zinc bis(1,4-didecylbenzo)-bis(2,3-pyrido) porphyrazines in IU-002 cells produce cell disruption that can be detected as a decrease in fluorescence.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"392090"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/392090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9367107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic polymers as drug-delivery vehicles in medicine.","authors":"Eberhard W Neuse","doi":"10.1155/2008/469531","DOIUrl":"https://doi.org/10.1155/2008/469531","url":null,"abstract":"<p><p>Cancerous diseases present a formidable health problem worldwide. While the chemotherapy of cancer, in conjunction with other treatment modalities, has reached a significant level of maturity, efficacious use of such agents is still restricted by numerous pharmacological deficiencies, such as poor water solubility, short serum circulation lifetimes, and low bioavailability resulting from lack of affinity to cancer tissue and inadequate mechanisms of cell entry. More critically still, most drugs suffer from toxic side effects and a risk of drug resistance. The class of platinum anticancer drugs, although outstandingly potent, is particularly notorious in that respect. Among the countless methods developed in recent years in an effort to overcome these deficiencies, the technology of polymer-drug conjugation stands out as a particularly advanced treatment modality. The strategy involves the bioreversible binding, conjugating, of a medicinal agent to a water-soluble macromolecular carrier. Following pharmacokinetic pathways distinctly different from those of the common, nonpolymeric drugs, the conjugate so obtained will act as a prodrug providing safe transport of the bioactive agent to and into the affected, that is, cancerous cell for its ultimate cell-killing activity. The present treatise will acquaint us with the pharmacological fundamentals of this drug delivery approach, applied here specifically to the metalorganic platinum-type drug systems and the organometallic ferrocene drug model. We will see just how this technology leads to conjugates distinctly superior in antiproliferative activity to cisplatin, a clinically used antitumor agent used here as a standard. Polymer-drug conjugation involving metal-based and other medicinal agents has unquestionably matured to a practical tool to the pharmaceutical scientist, and all indications point to an illustrious career for this nascent drug delivery approach in the fight against cancer and other human maladies.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"469531"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/469531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and photophysical properties of tetra- and octasubstituted phosphorous oxide triazatetrabenzcorrole photosensitizers.","authors":"Edith M Antunes,&nbsp;Tebello Nyokong","doi":"10.1155/2008/498916","DOIUrl":"https://doi.org/10.1155/2008/498916","url":null,"abstract":"<p><p>The synthesis of phosphorous oxide triazatetrabenzcorroles (TBC) tetra- (9, 11) or octa- (13) substituted on the ring with halogenated functional groups is reported. The complexes are not aggregated in dimethylsulfoxide (DMSO) and show solubility in solvents such as pyridine. The Q band absorption spectra of the complexes are red-shifted compared to unsubstituted PTBC. The latter complex shows a large triplet lifetime (1.7 milliseconds), higher than for MPc derivatives. The chlorinated derivatives show good triplet yields (Phi(T) approximately 0.46 and 0.36) and relatively long lifetimes (256 and 452 microseconds), respectively, for 11 and 13.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"498916"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/498916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9367106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid Metabolism.","authors":"Alois Kozubík,&nbsp;Alena Vaculová,&nbsp;Karel Soucek,&nbsp;Jan Vondrácek,&nbsp;Jaroslav Turánek,&nbsp;Jirina Hofmanová","doi":"10.1155/2008/417897","DOIUrl":"https://doi.org/10.1155/2008/417897","url":null,"abstract":"<p><p>The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"417897"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/417897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic-based antineoplastic drugs and their mechanisms of action.","authors":"Stephen John Ralph","doi":"10.1155/2008/260146","DOIUrl":"https://doi.org/10.1155/2008/260146","url":null,"abstract":"<p><p>Arsenic-based compounds have become accepted agents for cancer therapy providing high rates of remission of some cancers such as acute promyelocytic leukemia (APL). The mechanisms by which arsenic-containing compounds kill cells and reasons for selective killing of only certain types of cancer cells such as APLs have recently been delineated. This knowledge was gained in parallel with increasing understanding and awareness of the importance of intracellular redox systems and regulation of the production of reactive oxygen species (ROS) by controlling mitochondrial function. Many of the targets for the arsenic-containing compounds are mitochondrial proteins involved in regulating the production of ROS. Inhibition of these proteins by disulfide linkage of vicinal thiol groups often leads to increased production of ROS and induction of apoptotic signalling pathways. Sensitivity or resistance to the actions of arsenic-containing compounds on cancer cells and normal cells depends on the levels of transport systems for their uptake or efflux from the cells as well as their redox defence mechanisms. The exact mechanisms of arsenic toxicity as well as its anticancer properties are likely to be related and these aspects of arsenic metabolism are covered in this review. Greater understanding of the mechanisms of action of arsenic will help determine the risks of human exposure to this chemical. Novel organic arsenic-containing compounds and the lessons learned from studying their selective sensitivity in targeting dividing endothelial cells to inhibit angiogenesis raise the future possibility for designing better targeted antineoplastic arsenic-containing compounds with less toxicity to normal cells.</p>","PeriodicalId":18452,"journal":{"name":"Metal-Based Drugs","volume":"2008 ","pages":"260146"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2008/260146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}