Advances in Metallodrugs

Shahid-ul-Islam is a Principal Project Scientist at the Indian Institute of Technology Delhi, where he works on the chemistry of metal-based natural dyes using advanced technologies. He received his PhD in Chemistry from Jamia Millia Islamia (A Central University), New Delhi, India, in 2017. He has to his credit several research journal publications, patents and books with the Wiley-Scrivener imprint. Athar Adil Hashmi studied chemistry at Aligarh Muslim University, India and obtained his PhD in 1994. From 1990 to 2007 he held positions at the department of chemistry, Jamia Millia Islamia (Central University), New Delhi, India. Since April 2017 he is working as a visiting Professor at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. His work area includes organometallic chemistry, metal containing polymers and bio-inorganic chemistry. Along with his international publications, book chapters, he has guided 30 postgraduate projects and 13 PhD students. Salman Ahmad Khan received his PhD in Organic Chemistry from the Jamia Millia Islamia (JMI) (A Central University), New Delhi, India, in 2007. Since 2009 he has been with the Department of Chemistry, King Abdulaziz University, Jeddah, Saudi Arabia, where he is an Associate Professor. His current research interests include Heterocyclic Chemistry, Chromones, Chalcones, Anthraquinones, Photophysical, Physicochemical, Multi steps reactions, one pot multi component synthesis and Nanotechnology. Dr. Salman is an active researcher and has published more than 100 research articles in various reputed international journals.

• Preface xiii1 Metallodrugs in Medicine: Present, Past, and Future Prospects 1Imtiyaz Yousuf and Masrat Bashir1.1 Introduction 21.2 Therapeutic Metallodrugs 61.2.1 Anticancer Metallodrugs 61.2.1.1 Mechanism of Anticancer Action 71.2.2 Antimicrobial and Antiviral Metallodrugs 151.2.2.1 Antimicrobial Metallodrugs 151.2.2.2 Antiviral Metallodrugs 161.2.3 Radiopharmaceuticals and Radiodiagnostic Metallodrugs 171.2.4 Anti-Diabetic Metallodrugs 191.2.5 Catalytic Metallodrugs 221.3 Future Prospects 231.4 Conclusion 25References 262 Chemotherapeutic Potential of Ruthenium Metal Complexes Incorporating Schiff Bases 41Manzoor Ahmad Malik, Parveez Gull, Ovas Ahmad Dar, Mohmmad Younus Wani, Md Ikbal Ahmed Talukdar and Athar Adil Hashmi2.1 Introduction 422.2 Schiff Base Complexes of Ruthenium as Anticancer Agents 432.3 Conclusion 63References 643 Role of Metallodrugs in Medicinal Inorganic Chemistry 71Manish Kumar, Gyanendra Kumar, Arun Kant and Dhanraj T. Masram3.1 Introduction 723.2 Platinum Anticancer Drugs 743.2.1 Nucleophilic Displacement Reactions in Complexes of Platinum 803.2.2 Mode of the Interaction of Cisplatin Species With Nitrogen Donors of DNA Strand 803.2.3 Systemic Toxicity of Cisplatin 823.3 Copper-Based Anticancer Complexes 823.3.1 Copper is Essential for Health and Nutrition 823.3.2 Healthcare Applications of Copper 833.3.3 Copper and Human Health Disorders 833.3.3.1 Wilson’s Disease (WD) 843.3.3.2 Menkes’ Disease 853.3.4 Role of Copper Complexes as Potential Therapeutic Agents 853.3.4.1 Thiosemicarbazones-Based Complexes 863.3.4.2 Quinolones-Based Copper Complexes 883.3.4.3 Naphthoquinones 883.4 Zinc Anticancer Complexes 893.4.1 Biologically Importance of Zinc 903.4.2 Schiff Base Chemistry 923.4.2.1 Schiff Base and Their Metal Complexes 923.4.3 Zinc-Based Complexes 933.4.4 Top Food Sources of Zinc 943.4.5 Role of Zinc in Human Body 973.4.6 Zinc as a Health Benefit 983.4.7 Zinc in Alloy and Composites 1003.4.8 Zinc Supplementation as a Treatment 1003.4.8.1 Zinc Deficiency 1013.4.8.2 Zinc Toxicity 1023.4.8.3 Zinc and Viral Infections 1023.4.9 Gastrointestinal Effects 1033.5 Future Prospects of Metallodrugs 103References 1044 Ferrocene-Based Metallodrugs 115Hamza Shoukat, Ataf Ali Altaf and Amin Badshah4.1 Introduction 1154.2 Ferrocene-Based Antimalarial Agents 1174.2.1 Mechanism of Action 1184.3 Ferrocene-Based Antibacterial and Antifungal Drugs 1184.3.1 Schiff Base Derived Ferrocene Conjugates as Antibacterial Agents 1194.3.2 Ferrocenyl Guanidines as Antibacterial and Antifungal Agents 1214.3.3 Sedaxicene as Antifungal Agents 1224.4 Ferrocene-Based Anti-Tumor and Anti-Cancerous Drugs 1234.4.1 Ferricenium Salts as Anti-Tumor Agents 1244.4.2 Ferrocenylalkylazoles Active Anti-Tumor Drugs 1244.4.3 Ferrocene Conjugated to Peptides for Lung Cancer 1254.4.4 Ferrocenylalkyl Nucleobases Potential Anti-Cancerous Drugs 1264.4.5 Ferrocenyl Sub-Ordinates of Illudin-M 1264.4.6 Ferrocenyl Derivatives of Retinoids Potential Anti-Tumor Drug 1274.4.7 Targeting Breast Cancer With Selective Ferrocene-Based Estrogen Receptor Modulators (SERM) 1284.5 Conclusion 1314.6 Future of Ferrocene-Based Drugs 131References 1325 Recent Advances in Cobalt Derived Complexes as Potential Therapeutic Agents 137Manzoor Ahmad Malik, Ovas Ahmad Dar and Athar Adil Hashmi5.1 Introduction 1375.2 Cobalt Complexes as Potential Therapeutic Agents 1385.3 Conclusion 153References 1546 NO-, CO-, and H2S-Based Metallopharmaceuticals 157R. C. Maurya and J. M. Mir6.1 Introduction 1586.2 Signaling Molecules: Concept of “Gasotransmitter” 1606.2.1 Therapeutic Applications of NO, CO, and H2S 1626.2.1.1 Exogenous NO Donating Molecules 1636.3 NO Donors Incorporated in Polymeric Matrices 1676.3.1 Metal Nitrosyl Complexes 1686.3.1.1 Sodium Nitroprusside (SNP) 1686.4 Dinitrosyl Iron Thiol Complexes (DNICs) 1706.5 Photoactive Transition Metal Nitrosyls as NO Donors 1706.6 Exogenous CO Donating Molecules 1736.7 H2S Donating Compounds 1766.7.1 H2S Gas: A Fast Delivering Compound 1766.7.2 Sulfide Salts: Fast Delivering H2S Compounds 1776.7.3 Synthetic Moieties 1786.7.3.1 Slow-Delivering H2S Compounds 1786.7.3.2 H2S-Releasing Composite Compounds 1796.7.4 Naturally Occurring Plant Derived Compounds 1826.7.4.1 Garlic 1826.7.4.2 Broccoli and Other Cruciferous Vegetables 1846.8 Concluding Remarks and Future Outlook 185References 1867 Platinum Complexes in Medicine and in the Treatment of Cancer 203Rakesh Kumar Ameta and Parth Malik7.1 What is Cancer? 2037.1.1 Characteristic Features of Cancer Cells 2057.1.2 Definition of Anticancer Compound 2067.1.3 Anticancer Attributes of Pt Complexes 2077.1.4 Native State Behavior of Pt Complexes 2087.2 Compatibility of Pt Compounds in Cancer Treatment 2097.2.1 Significance of DNA as Primary Target 2097.2.2 Kinetics of DNA Binding Activities 2107.2.3 Structural and Regioselectivity of DNA Adducts 2107.2.4 Studies on Action Mechanism 2117.3 Pt Complexes as Anticancer Drugs 2147.3.1 DNA-Coordinating Pt(II) Complexes 2147.3.2 DNA-Covalently Binding Pt(II) Complexes 2197.3.3 Targeted Pt(II) Complexes 2227.3.4 Pt(IV) Prodrugs 2247.3.5 Multiple Action of Pt(IV) Prodrugs 2257.3.6 Targeted Pt(IV) Prodrugs 2287.3.7 Photodynamic Killing of Cancer Cell by Pt Complexes 2317.4 Conclusion 231Acknowledgments 232References 2328 Recent Advances in Gold Complexes as Anticancer Agents 247Mohammad Nadeem Lone, Zubaid-ul-khazir, Ghulam Nabi Yatoo, Javid A. Banday and Irshad A. Wani8.1 Introduction 2488.2 Evolution of Metal Complexes as Anticancer Agents 2508.3 Gold Complexes 2518.3.1 Complexes with Nitrogen Donar Ligands 2528.3.2 Complexes with Sulphur Donar Ligands 2548.3.3 Complexes with Phosphorus Donar Ligands 2558.3.4 Complexes with Sulphur-Phosphorus Donar Ligands 2568.3.5 Organometallic Gold Complexes 2598.3.6 Miscellaneous 2608.4 Nano-Formulations of Gold Complexes 2628.5 Future Challenges and Perspectives 2638.6 Conclusion 265Acknowledgements 266References 2669 Recent Developments in Small Molecular HIV-1 and Hepatitis B Virus RNase H Inhibitors 273Fenju Wei, Dongwei Kang, Luis Menéndez-Arias, Xinyong Liu and Peng Zhan9.1 Introduction 2739.1.1 Activity and Function of HIV and HBV RNases H 2749.1.2 The Metal-Chelating RNase H Active Site 2749.2 RNase H Inhibitors and Strategies in the Discovery of Active Compounds 2769.2.1 High-Throughput Screening 2769.2.2 Design Based on Pharmacophore Models 2789.2.3 Novel Inhibitors Obtained by Using “Click Chemistry” 2799.2.4 Dual-Target Inhibitors Against HIV-1 Integrase (IN) and RNase H 2809.2.5 Inhibitors Obtained by Using Privileged Fragment-Based Libraries 2829.2.6 RNase H Inhibitors in Natural Products 2839.2.7 Drug Repurposing Based on Privileged Structures 2849.3 Conclusion 286References 28710 The Role of Metals and Metallodrugs in the Modulation of Angiogenesis 293Mehmet Varol and Tuğba Ören Varol10.1 Introduction 29410.2 Metallodrugs in Anticancer Therapy 29710.3 Angiogenesis as a Substantial Target of Tumorigenesis 30010.4 Metals and Metallodrugs in Angiogenesis 30210.5 Concluding Remarks and Future Prospects 306References 30611 Metal-Based Cellulose: An Attractive Approach Towards Biomedicine Applications 319Kulsoom Koser and Athar Adil Hashmi11.1 Introduction 32011.2 History of Cellulose 32011.3 The Properties and Structure of Cellulose 32111.4 Modification of Cellulose 32211.4.1 Acid Hydrolysis 32211.4.2 Oxidation 32411.4.3 Esterification 32611.4.4 Amidation 33111.4.5 Carbamiation 33311.4.6 Etherification 33611.4.7 Nucleophilic Substitution 33911.4.8 Further Modification 34111.5 Present and Future Medical Applications of Cellulose as Well as Its Components 34411.5.1 Cellulose Used as Wound Dressing 34411.5.2 Dental Applications 34511.5.3 Engineering 34611.5.4 Controllable Drug Delivery System 34811.5.5 Blood Purification 34811.5.6 Wrapping Purpose 35011.5.7 Renal Failure 35111.6 Conclusion 351References 35212 Multifunctional Nanomedicine 363Nobel Tomar, Maroof A. Hashmi and Athar Adil Hashmi12.1 Introduction 36412.2 Diagnostics and Imaging 36612.3 Drug Delivery and Therapy 36912.3.1 Drug Delivery by Organic Nanomaterials 36912.3.1.1 Liposomal Drug Delivery 36912.3.1.2 Polymeric Drug Delivery 37112.3.1.3 Proteins and Peptides for Drug Delivery 3732.3.2 Drug Delivery by Inorganic Nanomaterials 37412.3.2.1 Metal and Metal Oxides 37412.3.2.2 Au NPs 37512.3.2.3 Carbon-Based NPs 37512.3.2.4 Silicon-Based Nanostructures for Drug Delivery 37812.3.3 Photo Therapy 37912.3.3.1 Photodynamic Therapy 38012.3.3.2 Photothermal Therapy 38112.3.4 Radiation Therapy 38312.3.5 Neutron Capture Therapy 38412.4 Regenerative Medicine 38512.5 Future Prospects and Conclusion 386References 387Index 403