Chemistry of Biologically Potent Natural Products and Synthetic Compounds

Shahid-ul-Islam is currently working as Principal Project Scientist at the Indian Institute of Technology Delhi. He worked as DST-SERB National Postdoctoral Fellow at Indian Institute of Technology Delhi, from 2017 to 2019. Then he joined same Institute as Principal Project Scientist where he works on natural products and chemistry of metal based natural dyes using advanced technologies. He has to his credit several research publications, patents and books including several with the Wiley-Scrivener imprint.J. A. Banday is associate professor and head, Department of Chemistry, National Institute of Technology (NIT) Srinagar, J&K, India. Dr. Banday has published a number of research papers in journals of international repute. He has produced and is supervising many M. Phil and Ph.D students. His research areas include isolation, modification & bio-evaluation of natural products, synthetic organic chemistry and medicinal importance of essential oils.

• Preface xiii1 Medicinal Importance of Plant Metabolites 1Sunita Panchawat and Chetna Ameta1.1 Introductory Note 11.2 Primary and Secondary Metabolites 31.3 Functional Roles of Secondary Metabolites 31.4 Source and Production of Secondary Metabolites 41.5 Classification of Secondary Metabolic Substances 71.5.1 Terpenes 81.5.2 Phenol-Based Compounds 91.5.3 Nitrogen-Containing Secondary Metabolites 101.5.3.1 Alkaloids 101.5.4 Secondary Metabolites Having Sulfur 111.6 Bioactivity of Secondary Metabolites 121.6.1 As Antioxidants 121.6.2 As Antimicrobials 131.6.3 As Anti-Diabetics Agents 131.7 Conclusion and Future Perspectives 14References 142 Advances in Natural Products-Based Antiviral Agents 21Zhipeng Fu, Luis Menéndez-Arias, Xinyong Liu and Peng Zhan2.1 Introduction 212.2 Anti-HIV Agents 222.2.1 Terpenes 232.2.2 Phenylpropanoids 242.2.3 Anthraquinones 252.2.4 Alkaloids 262.3 Natural Alkaloids With Activity Against HBV and HCV Infections 262.4 Anti-Influenza Virus Agents 282.5 Natural Products Active Against Herpesviruses 302.6 Natural Products Against Chikungunya Virus 312.7 Natural Products Targeting Dengue Virus 322.8 Natural Products Targeting Coronaviruses 332.9 Natural Products Against Other Viral Infections 362.10 Conclusion 37Acknowledgements 37References 373 Bioactive Component of Black Pepper-Piperine: Structure-Activity Relationship and Its Broad-Spectrum Activity—An Overview 43Arthi Sivashanmugam and Sivan VelmathiList of Abbreviations 443.1 Introduction: What is a Natural Product? 443.2 Black Pepper 483.2.1 Constituents of Black Pepper 513.2.2 Major Alkaloids of Black Pepper 513.3 Piperine—Active Molecule of Pepper 523.3.1 Isolation of Piperine 523.3.2 Piperine as Potential Drug 543.3.2.1 Metabolism of Piperine 543.3.2.2 Structure-Activity Relationship 553.3.2.3 Piperine and Piperine Analogs 593.3.2.4 Synergistic Activity of Piperine 723.4 Overall Summary and Conclusion 88References 894 Chemoenzymatic Synthesis of Pharmacologically Active Compounds Containing Chiral 1,2-Amino Alcohol Moiety 93Pankaj Gupta and Neha Mahajan4.1 Introduction 944.1.1 Chirality 944.1.2 Biocatalysis 964.1.2.1 Biocatalysis is Green and Sustainable 974.1.2.2 Industrial Applications of Biocatalysts 984.1.3 Vicinal Amino Alcohols 994.2 Synthetic Approaches Toward 1,2-Amino Alcohols 1024.2.1 Chemoenzymatic Synthesis of L-Norephedrine 1024.2.2 Synthesis of Valinol 1064.2.3 Chemoenzymatic Synthesis of Atazanavir 1074.2.4 Chemoenzymatic Synthesis of Levamisole 1074.2.5 Chemoenzymatic Synthesis of Optically Active (R)- and (S)-Aryloxypropanolamines 1084.2.6 Chemoenzymatic Preparation of Trans-(1R,2R)-and Cis (1S,2R)-1-Amino-2-Indanol 1124.2.7 Synthesis of Enantiomerically Pure 2-Aminopentane-1,3-Diol and 2-Amino-1,3,4-Butanetriol (ABT) 1134.2.8 Synthesis of Optically Active Cytoxazone 1154.2.9 Chemoenzymatic and Highly Integrated Synthesis of (S)-Tembamide 1164.2.10 Chemoenzymatic Synthesis of Paclitaxel C13 Side Chain 1174.3 Conclusion 118Acknowledgements 119References 1195 1,4-Naphthoquinone: A Privileged Structural Framework in Drug Discovery 133Umar Ali Dar, Mehnaz Kamal and Shakeel A. Shah5.1 Introduction 1335.1.1 Overview 1345.2 Various Targets of 1,4-Naphthoquinone for Its Actions 1355.2.1 Bacterial Topoisomerase II-DNA Gyrase for Antibacterial Action 1355.2.2 Mammalian Topoisomerases I and II for Antitumor Action 1355.2.3 HIV-1 Integrase and Proteinase for or Antiviral Action 1355.2.4 Dihydroorotate Dehydrogenase for Antimalarial Action 1365.2.5 Trypanothione and Trypanothione Reductase (TryR) for Leishmanicidal Action 1375.2.6 Mitochondrial Cytochrome (Coenzyme Q) for Antifungal Action 1375.3 Antifungal Activity 1375.4 Antibacterial Activities 1405.5 Anticancer Activity 1425.6 Antileishmanial Activity 1455.7 Antimalarial Activity 1475.8 Antiviral Activity 1495.9 Conclusion 149Acknowledgments 150References 1506 Design and Synthesis of Spirobiisoxazoline Derivatives 155K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali6.1 Introduction 1556.2 Literature Review on Spiroisoxazolines 1576.2.1 Chemistry 1576.2.2 Previous Approaches 1596.2.3 Biological Importance 1636.3 Literature Review on Quinones 1666.3.1 Chemistry 1666.3.2 Synthetic Approach 1676.3.3 Biological Importance 1696.4 Review on 1,3 Dipolar Cycloadditions of Oxime Chloride With Allenoates 1716.5 Present Work; Spirobiisoxazoline 1726.5.1 Results and Discussion 1726.5.1.1 Synthetic Studies 1726.5.1.2 Spectral Analysis 1766.5.2 Experimental Section 1786.6 Conclusion 179References 1797 Potential of Metal Complexes for the Treatment of Cancer: Current Update and Future Prospective 183Shipra Yadav7.1 Introduction 1847.2 Conclusion and Future Prospective 195References 1968 Design, Synthesis, and Biological Evaluation of Aziridynyl Quinone Derivatives 205K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali8.1 Introduction 2068.2 Aziridines 2078.2.1 Literature Review 2078.2.2 Synthetic Approach 2088.2.3 Biological Importance 2098.3 Quinones 2118.3.1 Literature Review 2118.3.2 Synthetic Approach 2138.3.3 Biological Importance 2158.4 Aziridinyl Quinone Derivatives 2178.4.1 Present Work 2198.4.2 Synthetic Studies 2208.4.2.1 Confirmation of Regioisomers 63 and 63a 2238.4.2.2 Confirmation of Regioselectivity for Diaziridinyl Compounds 2278.4.3 Biological Evaluation 2288.4.3.1 Antibacterial Activity 2298.4.3.2 Minimum Bactericidal Concentration 2308.4.3.3 Biofilm Inhibition Assay 2338.4.3.4 Antifungal Activity 2358.4.3.5 Minimum Fungicidal Concentration 2378.4.3.6 Cytotoxic Activity 2378.4.4 Experimental Section 2418.4.4.1 Chemistry 2418.4.4.2 Biological Studies 2438.5 Conclusion 246References 2479 Exploring the Promising Anticancer and Antimicrobial Potential of Bioactive Triazoles and Their Related Compounds 251Manzoor Ahmad Malik, Ovas Ahmad Dar, Nitu Singh, Gulshitab Aalam and Athar Adil Hashmi9.1 Introduction 2529.2 Anticancer Triazole Derivatives 2569.3 Antimicrobial Triazole Derivatives 2679.4 Conclusion 275References 27610 Fused Triazolo Isoquinoline Derivatives—Design, Synthesis, and Biological Evaluation 281K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali10.1 Introduction 28210.2 Literature Review on 1,2,4 Triazoles 28310.2.1 Chemistry 28310.2.2 Synthetic Approach 28410.2.3 Biological Importance 28710.3 Review on Isoquinoline and Fused Triazolo Isoquinolines 29210.4 Present Work 29410.5 Results and Discussion 29410.5.1 Synthetic Studies 29410.5.1.1 Confirmation of Regioisomer 29810.5.2 Spectral Analysis 29910.5.2.1 1H NMR Spectral and Mass Analysis 29910.5.2.2 13C NMR Spectral Analysis 29910.5.3 Biological Studies 29910.5.3.1 Antifungal Activity 30010.5.3.2 Minimum Fungicidal Concentration 30010.5.3.3 Ergosterol Biosynthesis Inhibition 30310.5.3.4 Cytotoxic Activity 30510.5.4 Molecular Docking Studies 30510.5.5 Experimental Section 30910.5.5.1 Chemistry 30910.5.5.2 Biological Studies 31110.5.6 Molecular Modeling Procedure 31410.6 Conclusion 314References 31511 Amide as a Potential Pharmacophore for Drug Designing of Novel Anticonvulsant Compounds 319Mehnaz Kamal, Talha Jawaid, Umar Ali Dar and Shakeel A. Shah11.1 Introduction 32011.2 Chemistry of Amides 32111.2.1 Synthesized Methods Utilized for Amide Bond Formation 32111.2.2 Amide Pharmacophore Containing Anticonvulsant Drug 32211.2.3 Anticonvulsant Activity 32211.3 Conclusion 337Acknowledgments 337References 33712 Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide as Biologically Important Signaling Molecules With the Significance of Their Respective Donors in Ophthalmic Diseases 343R. C. Maurya and J. M. Mir12.1 Introduction 34412.2 A Meaningful Introduction to Gasotransmitters 34612.3 Biosynthesis and Target of NO, CO, and H2S 34712.3.1 Biological Synthesis and Target of NO 34712.3.2 Biological Production and Target of CO 34912.3.3 Biosynthesis and Target Sites of H2S 35312.4 Gasotransmitters in the Mission of Vision (Eye-Health Contribution) 35712.4.1 NO News is Good News for Eyes: NO Donors for the Treatment of Eye Diseases 35712.4.1.1 Nitric Oxide Releasing Molecules (NORMS) and the IOP 35912.4.2 Carbon Monoxide, CORMS, and the Ocular System 36312.4.3 Hydrogen Sulfide and Ophthalmic Diseases 36712.5 Concluding Remarks and Future Outlook 368References 36813 Influence of rol Genes for Enhanced Biosynthesis of Potent Natural Products 379Erum Dilshad, Huma Noor, Nabgha Nosheen, Syeda Rehab Gilani, Umar Ali and Mubarak Ali Khan13.1 Introduction 38013.2 Secondary Metabolites or Natural Products 38113.2.1 Classes of Natural Products (Secondary Metabolites) 38213.2.1.1 Terpenoids 38213.2.1.2 Phenolic Compounds 38313.2.1.3 Alkaloids 38313.2.2 Strategies to Enhance Natural Products 38313.2.2.1 Plant Cell Culture (Somaclonal Variation) 38413.2.2.2 Genetic Transformation of Plant Cell 38413.2.2.3 Multiple Gene Transfer Through Improving Vectors 38513.2.3 Genetic Engineering/Metabolic Engineering 38513.3 rol Genes 38613.3.1 Origin of rol Genes 38713.3.2 Types of rol Genes 38813.3.2.1 The rolA Gene 38813.3.2.2 The rolB Gene 38913.3.2.3 The rolC Gene 39013.3.2.4 The rolD Gene 39113.3.3 The Combined Effect of Genes rol on Secondary Metabolism 39213.4 Mechanism of Action of rol Genes 39313.4.1 How rol Genes Regulate ROS Production and Mediate Secondary Metabolites Production 39313.4.1.1 Agrobacterium (rol Gene) and ROS 39313.4.1.2 Plants Secondary Metabolism and ROS 39413.4.1.3 Stabilization of Secondary Metabolites Biosynthesis Through rol Genes 39513.5 Impact of rol Gene on Different Secondary Metabolites 39513.5.1 Impact of rol Gene on Alkaliods 39513.5.2 Impact of rol Genes on Flavonoids 39613.5.3 Impact of rol Genes on Terpenoids 39613.6 Conclusion 397References 397Index 405