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CHEMISTRY AND BIOLOGICAL ACTIVITIES OF IVERMECTIN The book focuses on the biological activities of ivermectin as well as the significant global utility of IVM since it was first used about 35 years ago.
Ivermectin (IVM) is a "wonder drug" containing a 16-membered macrocyclic lactone ring system in its structure and derived from the family of avermectins. It was isolated by the fermentation of the soil microorganism Streptomyces avermitilis by Satoshi Omura in 1960 and studied by William C. Campbell in 1981, which allowed for its treatment of onchocerciasis (River Blindness) in Africa. Both scientists subsequently received the 2015 Nobel Prize in Physiology or Medicine. It was approved by the FDA in 1997 for the treatment of Strongyloidiasis and crusted scabies in AIDS patients. After that, IVM has attracted the tremendous attention of the scientific community and has been used for diverse purposes, including as an inhibitor of the causative virus (SARS-CoV-2).
The chief purpose of this volume is to focus on the chemistry and biological activities of ivermectin. The chapters have been arranged in a systematic manner, starting from the historical background and synthesis of IVM to the pharmacological and environmental aspects, followed by diverse applications. Although the usage of ivermectin for the treatment of COVID-19 remains under investigation and controversial, one of the chapters is dedicated to its use. The anti-parasitic, anti-malarial, anti-cancer, and anti-inflammatory activities of IVM are discussed in detail. The anthelminthic and insecticidal roles of IVM are briefly described and there are several cases of IVM in dermatology.
Audience
Researchers, scientists, and postgraduate students working in the fields of organic synthesis, medicinal chemistry, medical science, pharmacy, biotechnology and biomedical sciences.
Contents
Preface xi
1 Introduction to Ivermectin 1
Aeyaz Ahmad Bhat, Atif Khurshid Wani, Tahir ul Gani Mir and Nahid Akther
1.1 Introduction 1
1.2 Sources and Synthesis 3
1.3 Pharmacological Potential of Ivermectin 4
1.4 Ivermectin's Beneficial Role in Cattle 8
1.5 Ivermectin in the Treatment of COVID-19 8
1.6 Toxicity of Ivermectin 10
1.7 Conclusion 13
2 Historical Background of and Synthetic Approaches to Ivermectin (IVM) and its Homologues 23
Shakeel Alvi, Mohd Kamil Hussain and Rashid Ali
2.1 Introduction 24
2.2 Synthetic Approaches Towards the Construction of IVM and Analogues 29
2.3 Biosynthesis 29
2.4 Chemical Synthetic Pathway 33
2.5 Crystal Structure 42
2.6 Conclusion and Outlook 42
3 Ivermectin as a Repurposed Drug for COVID-19 47
Hari Madhav, Mohammad Rehan, Nasimul Hoda and Ehtesham Jameel
3.1 Introduction 47
3.2 Symptoms of COVID-19 50
3.3 Repurposing of the Drugs 52
3.4 Repurposed Drugs for COVID-19 52
3.5 Repurposing of Ivermectin for COVID-19 53
3.6 Proposed Possible Mechanism of Action 54
3.7 SARS COVID-19 Clinical Studies with Ivermectin 55
3.8 Conclusions 59
3.9 Acknowledgments 60
4 Ivermectin as an Anti-Parasitic Agent 69
Areeba Rahman, Abdulaziz S. Alouffi, Mohammad Husain and Abdur Rub
4.1 Introduction 70
4.2 Use of Ivermectin Against Various Human Parasitic Infections 76
4.3 Mode of Action Against Various Parasites 83
4.4 Conclusions 83
4.5 Acknowledgements 84
5 Emerging Paradigm of Ivermectin and its Hybrids in Elimination of Malaria 93
Iram Irfan, Diksha Shahi, Mukesh C. Joshi, Shailja Singh and Mohammad Abid
5.1 Introduction 94
5.2 Malaria 95
5.3 Life Cycle of Malaria 100
5.4 Drug Against Hepatic Malarial Stage 105
5.5 About Ivermectin 106
5.6 Designing and Synthesis of Ivermectin Inhibitors 107
5.7 Conclusions 112
5.8 Acknowledgments 113
6 Ivermectin: A Potential Repurposed Anti-Cancer Therapeutic 121
Mohd Kamil Hussain, Rashid Ali, Shakir Ahamad, Mohammad Faheem Khan and Mohammad Saquib
6.1 Introduction 122
6.2 Mechanism of Anti-Carcinogenesis 124
6.3 Activation of Chloride Ion Channels 125
6.4 Anti-Mitotic Effect and Inhibition of Angiogenesis 127
6.5 Inhibition of Mitochondrial Respiration 127
6.6 Inhibitor of Cancer Stem Cells (CSCs) 128
6.7 Induction of Immunogenic Cell Death (ICD) 128
6.8 Epigenetic Modulator 129
6.9 Induction PAK1-Mediated Cytostatic Autophagy 129
6.10 Inhibition of P-glycoprotein (P-gp) 130
6.11 Inhibition of Yes-Associated Protein 1 (YAP1) 130
6.12 Inhibition of RNA Helicase 131
6.13 Caspase-Dependent Apoptosis 132
6.14 Activation of Transcription Factor E3 (TFE3) 132
6.15 Inhibition of Wnt-TCF Pathway Responses 132
6.16 Conclusions 133
7 Ivermectin as an Anti-Inflammatory Agent 141
Mudasir Nabi Peerzada and Saurabh Verma
7.1 Introduction 141
7.2 Ant-Inflammatory Action of Ivermectin 147
7.3 Conclusions 155
8 Ivermectin: An Anthelminthic and Insecticide 163
Manisha Arora Pandit and Tarkeshwar
8.1 Introduction 164
8.2 Ivermectin as an Anthelmintic 165
8.3 Insecticidal Activity of Ivermectin 176
9 Potential Applications of Ivermectin (IVM) in Dermatology 199
Vikrant Jayant and Rashid Ali
9.1 Introduction 200
9.2 Mechanism of Action, Toxicity, and Side Effects of IVM 203
9.3 Motivational Approach of IVM in the Treatment of Skin 206
9.4 Role of IVM with Good Anti-Parasitic Properties Against the Infection of Skin 212
9.5 Importance of IVM as an Anti-Cancer or Anti-Tumor Agent in Curing the Skin 219
9.6 Social Value of IVM in the Medical Care of Red Scrotum Syndrome (RSS) 220
9.7 Utility of IVM as an Anti-Inflammatory Drug in the Treatment of Skin-Related Issues 221
9.8 Conclusions 224
10 Antiviral Uses of Ivermectin 231
Shabnam Kawoosa, Rabiah Bashir, Sheeba Nazir, Zubaid-ul-Khazir Rather, Gulam Nabi Yatoo and Nisar Ahmad Khan
10.1 Introduction 231
10.2 Mechanism of Action of Ivermectin 233
10.3 Anti-Viral Effects Against Various DNA and RNA Viruses 236
10.4 Conclusion 242
11 Toxicology, Safety, and Environmental Aspects of Ivermectin 247
Ayesha Akhtar, Nasreen A. Mazumdar and Afreen Inam
11.1 Introduction 247
11.2 Ivermectin's Antiparasitic Activity 249
11.3 Pharmacology 250
11.4 Adverse Effects in Humans and Animals 251
11.5 Ivermectin and Ectoparasites 255
11.6 Environmental Impact and Biodegradation of Ivermectin 258
11.7 Conclusion 259
References 259
Index 265
