Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine

METALLOTHERAPEUTIC DRUGS AND METAL-BASED DIAGNOSTIC AGENTS......Page 4
Contents......Page 8
List of Contributors......Page 29
Preface......Page 40
1.1 Introduction......Page 44
1.2 The Inorganic Chemistry of Lithium......Page 45
1.3.1 The history of lithium therapeutics......Page 46
1.3.2 Lithium and the body......Page 47
1.4.1 Glycogen synthase kinase-3......Page 48
1.4.2 Inositol phosphate signalling......Page 51
1.5.1 Bipolar disorder and schizophrenia......Page 53
1.5.2 Alzheimer’s disease......Page 55
1.5.4 Adverse effects......Page 57
References......Page 58
2.1 Boron Neutron Capture Therapy......Page 62
2.2.1 DNA binders......Page 65
2.2.2 Boron-containing amino acids and related peptides......Page 67
2.2.3 Boron-containing nucleic acid precursors......Page 70
2.3 Phosphates, Phosphonates and Phosphoramidates......Page 74
2.5 Boron Analogues of Pyrophosphates......Page 76
2.6 Boronated Polyamines......Page 77
2.8 Lipoproteins......Page 79
2.9 Lipids and Phospholipids......Page 80
2.11 Cyclic Thiourea Derivatives......Page 81
2.13 Hydantoins and Barbiturates......Page 82
2.14 Oligonucleotide Antisense Agents......Page 83
2.15 Hormones......Page 85
2.16 Liposomes......Page 87
2.17 Conclusions......Page 88
References......Page 89
3.1 Introduction......Page 94
3.2.1 Gestational hypertension, preeclampsia and eclampsia......Page 96
3.2.2 Asthma......Page 97
3.2.3 Stroke......Page 98
3.2.4 Acute myocardial infarction......Page 100
3.2.5 Arrhythmias......Page 103
3.2.6 Miscellaneous......Page 104
References......Page 105
4.1 Introduction......Page 108
4.2.1 Alum......Page 109
4.2.2 Al(OH)(3)......Page 110
4.3.1 Aluminum hydroxide......Page 112
4.3.3 Peptic ulcer disease......Page 113
4.4 Phosphate Binders......Page 116
4.5 Alginate Raft Formulations......Page 118
4.7 Metabolic Diseases and Aluminum......Page 120
4.8 Anti-malarial Substances......Page 121
4.9 Potential Aluminum Toxicity......Page 122
References......Page 123
5.1 Introduction......Page 126
5.2.1 O-, S- and N-Silylation......Page 127
5.2.2 C-Silylation......Page 132
5.3 Sila Analogues......Page 135
5.4 Specific Organosilicon Compounds......Page 137
References......Page 139
6.1 Introduction......Page 152
6.2 Calcium Homeostasis......Page 153
6.3 Hormonal Regulation of Calcium Metabolism......Page 154
6.4 Optimal Amount of Dietary Calcium Intake and Benefits of Calcium Supplementation......Page 155
6.5 Osteoporosis......Page 158
6.6 Hypertension......Page 159
6.7 Hypertension in Pregnancy and Preeclampsia......Page 161
6.9 Weight Control and Regulation of Body Fat......Page 162
6.10 Periodontal Disease......Page 163
6.12 Calcium Supplements: Side Effects......Page 164
6.13 Conclusions......Page 165
References......Page 166
7.1 Introduction......Page 168
7.2 The Biochemistry of Titanium......Page 169
7.3 Titanium Anti-cancer Drugs......Page 170
7.4.1 Chemistry and anti-cancer activity......Page 173
7.4.2 Isomer abundance of budotitane......Page 174
7.4.3 Reaction with biomolecules......Page 176
7.4.5 Clinical investigations......Page 177
7.5.1 Chemistry and anti-cancer activity......Page 178
7.5.2 Reaction with biomolecules......Page 179
7.5.3 Animal studies......Page 180
7.5.5 Perspectives of titanocene dichloride......Page 181
7.6 Conclusions......Page 182
References......Page 183
8.1 Chemistry of Vanadium......Page 186
8.3 The Role of Insulin in Glucose Metabolism......Page 187
8.4 Vanadium Complexes with Biological Activity......Page 188
8.5 Biological Activity and Toxicity of Various Vanadium(IV/V) Compounds......Page 191
8.6 Speciation of VI(IV) Complexes in Biological Fluids......Page 192
8.7 Possible Mechanism for in vivo Vanadium Action......Page 196
8.8 Conclusion......Page 198
References......Page 199
9.1 Prevalence in the Environment......Page 202
9.4 MnSOD......Page 203
9.5.1 Animals......Page 204
9.6 Toxicity......Page 205
9.7 Therapeutic Manganese-Related Agents......Page 206
9.8.1 Arthritis......Page 208
9.8.2 Cancer......Page 209
9.8.3 Cardiovascular diseases......Page 210
9.8.5 Diabetes......Page 211
9.8.7 Human immunodeficiency virus......Page 212
9.8.8 Inflammatory pain and response......Page 213
9.8.10 Osteoporosis......Page 214
9.8.12 Premenstrual syndrome......Page 215
9.8.13 Shortened life span (premature aging)......Page 216
9.9 Magnetic Resonance Imaging (MRI)......Page 217
Acknowledgements......Page 218
References......Page 219
10.1 Introduction......Page 222
10.2 Ferrocene......Page 223
10.4 Ferrocene in Drug Design......Page 224
10.4.1 Examples where introduction of ferrocene has resulted in a loss or no change in activity......Page 225
10.4.2 Examples where introduction of ferrocene has resulted in enhanced activity or a change in activity profile......Page 226
10.5 Ferrochloroquine......Page 228
10.6 Other Ferrocenyl Anti-plasmodial Agents......Page 234
10.7 Organoiron as Anti-cancer Agents......Page 236
10.8 Conclusions......Page 240
References......Page 241
11.1 Introduction......Page 244
11.2.2 Topoisomerase II inhibitors......Page 245
11.2.3 Heme oxygenase-1 inducers......Page 246
11.3.1 Cobalt(III) polypyridyl complexes......Page 247
11.3.2 Cobalt(III) bleomycin complexes......Page 249
11.3.3 Cobalt(III) polyamine complexes......Page 251
11.4.1 Cobalamin conjugates as drug delivery devices......Page 252
11.4.2 Hypoxic selective agents......Page 254
11.4.3 PET imaging agents......Page 256
References......Page 257
12.1 Introduction......Page 262
12.2 Copper-Purine Derivatives Complexes......Page 263
12.3 Copper-Thiosemicarbazone Complexes......Page 266
12.5 Copper-Imidazole Derivatives Complexes......Page 273
12.6 Copper-Polycarboxylate Complexes......Page 276
Acknowledgements......Page 277
References......Page 278
13.2 Functions......Page 280
13.3 Zinc Deficiency......Page 281
13.3.3 Growth retardation......Page 282
13.4.3 Malaria......Page 283
13.5.2 Intake recommendations......Page 284
13.6.3 Human immunodeficiency virus (HIV) infection......Page 286
13.6.5 Wound healing......Page 287
13.8 Zinc Status and Its Relevance to Cancer......Page 288
13.8.1 Zinc deficiency and oxidative stress......Page 289
13.8.2 Zinc and DNA repair......Page 290
13.8.3 Zinc and prostate cancer......Page 292
13.9.1 Toxicity......Page 294
References......Page 295
14.1 Introduction......Page 302
14.2.1 Aqueous biochemistry......Page 303
14.2.2 Gallium and iron......Page 304
14.2.3 Mechanisms of action......Page 307
14.3.1 Gallium nitrate and citrated gallium nitrate......Page 308
14.3.3 Gallium 8-quinolinolate......Page 312
14.3.4 Gallium maltolate......Page 313
14.3.5 Other gallium compounds......Page 314
References......Page 316
15.1 Introduction......Page 322
15.2.1 2-Carboxyethylgermanium sesquioxide......Page 325
15.2.2 Spirogermanium......Page 328
15.2.3 Germatranes......Page 329
15.2.4 Germanium modified organic compounds......Page 331
References......Page 333
16.1 Introduction......Page 340
16.2 Chemistry of Arsenic......Page 342
16.3 Mechanisms of Action......Page 343
16.3.1 Modulation of PML and PML–RARa genes......Page 344
16.3.2 Induction of intracellular reactive oxygen species (ROS)......Page 345
16.3.4 Roles of glutathione......Page 346
16.3.6 Involvement of p53......Page 347
16.3.8 Other mechanisms of arsenic-induced apoptosis......Page 348
16.4.2 Metabolism......Page 349
16.5 Toxic Side Effects of As(2)O(3)......Page 350
16.7 Summary and Conclusions......Page 351
References......Page 352
17.1 Introduction to Selenium and its Biochemistry......Page 356
17.2 Diseases Associated with Selenium Deficiency......Page 358
17.2.2 Keshan disease......Page 359
17.3.1 Arsenism......Page 360
17.3.2 Cancer prevention......Page 361
17.4.1 Anti-oxidants and anti-inflammatory agents......Page 364
17.4.2 Anti-cancer......Page 367
17.4.4 Anti-virals and anti-bacterials......Page 370
References......Page 371
18.1 Overview......Page 376
18.2 Technetium: Historical Accounts and Properties Relevant to Nuclear Medicine......Page 377
18.3.1 Tc-essential compounds......Page 379
18.3.2 Tc-tagged compounds......Page 381
18.4 Peptide-Targeted Radiopharmaceuticals......Page 386
18.5.1 Bioorganometallic chemistry......Page 387
18.5.2 Tc and solid supports......Page 388
18.5.3 Technetium-94m......Page 392
18.6 Outlook......Page 393
References......Page 395
19.1 Introduction......Page 402
19.2 Ruthenium Complexes that Mimic Platinum Drugs......Page 403
19.2.1 Chloro-ammino derivatives......Page 404
19.2.2 Dimethyl-sulfoxide complexes......Page 405
19.2.3 Complexes with mixed chloride and heterocyclic ligands......Page 407
19.3 Design of New Anti-cancer Compounds based on the Photoreactivity of Polyazaaromatic Ruthenium(II) Complexes......Page 408
19.3.1 Energy transfer processes leading to photo-cleavages......Page 410
19.3.2 Photoelectron transfer processes leading to DNA cleavages......Page 411
19.3.3 Photoelectron transfer processes leading to photoadduct formation......Page 414
19.4 Targeting Base Residues of Specific Sequences......Page 416
19.5 Conclusions......Page 418
References......Page 419
20.2 Anti-tumor Activity of Rhodium Complexes......Page 422
20.2.1 Rhodium(I) complexes......Page 423
20.2.2 Rhodium(II) complexes......Page 424
20.2.3 Rhodium(III) complexes......Page 428
20.3 Anti-bacterial and Anti-parasitic Activity......Page 431
20.4 Radiorhodium Agents......Page 433
20.5 Photochemotherapy......Page 434
20.6 Toxicity of Rhodium Complexes......Page 435
References......Page 437
21.1 Introduction......Page 442
21.2.1 Sulfur-donor ligands......Page 443
21.2.2 Metal complexes of drugs used as ligands......Page 447
21.2.3 Palladium(II) complexes with Schiff base ligands......Page 448
21.2.4 Miscellaneous......Page 449
21.3.1 Sulfur-donor ligands......Page 450
21.3.2 Nitrogen and other donor atoms......Page 453
21.4 Concluding Remarks......Page 457
References......Page 458
22.1 Introduction......Page 464
22.3 Anti-tumour Pre-screening......Page 465
22.4 Early In Vitro Cytotoxicity Testing of Diorganotin Carboxylates......Page 466
22.5 The Di-n-Butyltin Analogue of Carboplatin......Page 468
22.6 Anti-tumour Potential of Triorganotin Carboxylates......Page 469
22.7 Anti-tumour Screening of Organotin Derivatives of Biologically Relevant Substrates......Page 470
22.9 Anti-tumour Potential of Boron-Containing Organotin Carboxylates......Page 471
22.10 Anti-tumour Potential of Organotin Carboxylates-Containing Polyoxaalkyl Moieties......Page 473
22.12 Other Therapeutic Potential of Organotin Compounds......Page 474
22.13 Therapeutic Potential of Tin Compounds Without Tin-to-Carbon Bonds......Page 476
References......Page 478
23.2 The Chemistry of Antimony......Page 484
23.3.1 Historic view of antimony drugs......Page 486
23.3.2 Applications of antimony drugs as anti-leishmanial agents......Page 487
23.3.3 Other medicinal applications......Page 488
23.4.1 Pharmacology and human toxicology of antimony drugs......Page 490
23.4.2 Pharmacokinetics studies and clinical aspect of antimony drugs......Page 491
23.5.2 In vitro and in vivo reduction of antimony(V) drugs......Page 492
23.5.3 Interaction of antimony(III) compounds with thiolate molecules......Page 493
23.5.4 Inhibition of topoisomerase I from Leishmania donovani and formation of DNA-protein complexes by Sb(V)......Page 496
23.5.6 Interference of the exclusive purine scavenge pathway of Leishmania......Page 497
23.5.7 Modulation and increase of cellular signaling of the host macrophage as a means of intracellular Leishmania elimination......Page 498
References......Page 500
24.1 Introduction......Page 506
24.2 Synthetic Aspects of Rhenium Radiopharmaceuticals......Page 509
24.3.1 Complexes with oxo-cores......Page 510
24.3.2 Complexes with cores containing metal–nitrogen multiple bonds......Page 515
24.3.3 Complexes of the Re(I) tricarbonyl core......Page 517
24.3.4 Organometallic approaches......Page 522
24.3.5 Miscellaneous approaches......Page 523
24.4.1 Bone-targeting phosphonate complexes......Page 525
24.4.2 [Re(V)-oxo(DMSA)]......Page 526
24.4.3 Rhenium agents for endovascular radiation therapy......Page 527
24.5 Summary......Page 528
References......Page 529
25.1 Introduction, Anti-tumor Activity of Cisplatin......Page 532
25.2 Anti-tumor Activity of Carboplatin, Oxaliplatin and Nedaplatin......Page 533
25.3 Mechanism of Action of Cisplatin......Page 534
25.4 Mechanism of Action of Carboplatin, Oxaliplatin and Nedaplatin......Page 537
25.5 Activation of trans Geometry......Page 538
25.6 Polynuclear Platinum Compounds......Page 541
25.7 Platinum(IV) Compounds......Page 542
25.8 Targeted Analogues......Page 543
25.9 Anti-viral Activity......Page 544
25.11 Conclusions......Page 545
References......Page 546
26.2.1 Physical properties of the element......Page 550
26.2.3 Oxidation states and stereochemistries of gold complexes......Page 551
26.3.1 Historical perspective......Page 553
26.3.2 Gold therapy for rheumatoid arthritis......Page 554
26.4.2 Gold in cells: The thiol-shuttle model......Page 557
26.4.3 Cyanide metabolites......Page 558
26.5.1 Motivation for drug development......Page 559
26.5.2 Anti-tumour properties of gold drugs......Page 560
26.5.4 Auranofin analogues......Page 561
26.5.5 Gold(III) complexes......Page 563
26.6.1 Anti-microbial activity......Page 564
26.6.2 Anti-malaria activity......Page 565
26.6.3 Treatment of bronchial asthma......Page 566
References......Page 567
27.2 Bismuth-Based Therapeutics......Page 572
27.3 Fundamental Aspects of Bismuth Chemistry and Methods of Characterization......Page 573
27.4 Hydroxycarboxylate Complexes of Bismuth......Page 574
27.5 Development of Bioactive Bismuth Compounds......Page 577
27.6 Interactions of Bismuth Compounds with Biological Molecules......Page 580
References......Page 582
28.1 Generalities on Magnetic Resonance Imaging (MRI) and Paramagnetic Contrast Agents......Page 584
28.2 Determinants of the Relaxivity of Paramagnetic Metal Complexes......Page 587
28.3 Responsive Agents......Page 591
28.3.1 pH sensitive agents......Page 592
28.3.2 Agents sensitive to the redox potential......Page 594
28.3.3 Enzyme responsive agents......Page 595
28.4 Targeting Cells with Gd(III) Chelates......Page 597
References......Page 602
Index......Page 604