Sb Antimony in Medicine

Siucheong Yan, Lan Jin and Hongzhe Sun

23«1 Introduction 441

23«2 The Chemistry of Antimony 441

23«3 Antimony in Medicine 443

23.3.1 Historic view of antimony drugs 443

23.3.2 Applications of antimony drugs as anti-leishmanial agents 444

23.3.3 Other medicinal applications 445

23*4 Pharmacology, Toxicology and Metabolism of Antimony Drugs 447

23.4.1 Pharmacology and human toxicology of antimony drugs 447

23.4.2 Pharmacokinetics studies and clinical aspect of antimony drugs 448

23«5 Possible Mechanism of Action of Antimony Drugs: Interaction of Antimony with Biologically Relevant Molecules 449

23.5.1 General hypothesis on the mechanisms of action of antimony anti-leishmanial compounds 449

23.5.2 In vitro and in vivo reduction of antimony(V)

drugs 449

23.5.3 Interaction of antimony(III) compounds with thiolate molecules 450

23.5.4 Inhibition of topoisomerase I from Leishmania donovani and formation of DNA-protein complexes by SbV 453

23.5.5 Antimony-mediated DNA fragmentation, apoptosis and Ca2 + -related programmed cell death in Leishmania 454

23.5.6 Interference of the exclusive purine scavenge pathway of Leishmania 454

23.5.7 Modulation and increase of cellular signaling of the host macrophage as a means of intracellular Leishmania elimination 455

23.6 Concluding Remarks

Abbreviations 457

Acknowledgement 457

References 457

24 75Re Therapeutic Rhenium

Radiopharmaceuticals 463

Jonathan R. Dilworth and Paul S. Donnelly

24.1 Introduction 463

24.2 Synthetic Aspects of Rhenium Radiopharmaceuticals 466

24.2.1 Complexes of bifunctional ligands 467

24.3 The Radiopharmaceutical Chemistry of

Rhenium 467

24.3.1 Complexes with oxo-cores 467

24.3.2 Complexes with cores containing metal-nitrogen multiple bonds 472

24.3.3 Complexes of the Re(I) tricarbonyl core 474

24.3.4 Organometallic approaches 479

24.3.5 Miscellaneous approaches 480

24*4 'First-Generation' Rhenium Agents 482

24.4.1 Bone-targeting phosphonate complexes 482

24.4.3 Rhenium agents for endovascular radiation therapy 484

24.4.4 Rhenium agents for radiation synovectomy 485

24*5 Summary 485

References 486

25 7ßpt Platinum-Based Drugs 489

Viktor Brabec and Jana Kasparkova

25*1 Introduction, Anti-tumor Activity of Cisplatin 489

25*2 Anti-tumor Activity of Carboplatin, Oxaliplatin and Nedaplatin 490

25*3 Mechanism of Action of Cisplatin 491

25«4 Mechanism of Action of Carboplatin,

Oxaliplatin and Nedaplatin 494

25*5 Activation of trans Geometry 495

25*6 Polynuclear Platinum Compounds 498

25*7 Platinum(IV) Compounds 499

25*8 Targeted Analogues 500

25*9 Anti-viral Activity 501

25*10 Combinations of Platinum Complexes with

Other Agents 502

25*11 Conclusions 502

Acknowledgements 503

References 503

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