Chemistry of Biologically Potent Natural Products and Synthetic Compounds

In view of their promising biological and pharmaceutical activities, natural product inspired and heterocyclic compounds have recently gained a reputation in the field of medicinal chemistry. Over the past decades, intensive research efforts have been ongoing to understand the synthesis, biochemistry and engineering involved in their preparation and action mechanisms. Several novel natural product derivatives, heterocyclic and other synthetic compounds, have been reported to have shown interesting biological activities including anticancer, antimicrobial, anti-inflammatory, anti-glycemic, anti-allergy and antiviral etc. Chemistry of Biologically Potent Natural Products and Synthetic Compounds provides up-to-date information on new developments and most recent medicinal applications of the natural products and derivatives, as well as the chemistry and synthesis of heterocyclic and other related compounds.

Table of Contents:
Preface xiii 1 Medicinal Importance of Plant Metabolites 1 Sunita Panchawat and Chetna Ameta 1.1 Introductory Note 1 1.2 Primary and Secondary Metabolites 3 1.3 Functional Roles of Secondary Metabolites 3 1.4 Source and Production of Secondary Metabolites 4 1.5 Classification of Secondary Metabolic Substances 7 1.5.1 Terpenes 8 1.5.2 Phenol-Based Compounds 9 1.5.3 Nitrogen-Containing Secondary Metabolites 10 1.5.3.1 Alkaloids 10 1.5.4 Secondary Metabolites Having Sulfur 11 1.6 Bioactivity of Secondary Metabolites 12 1.6.1 As Antioxidants 12 1.6.2 As Antimicrobials 13 1.6.3 As Anti-Diabetics Agents 13 1.7 Conclusion and Future Perspectives 14 References 14 2 Advances in Natural Products-Based Antiviral Agents 21 Zhipeng Fu, Luis Menéndez-Arias, Xinyong Liu and Peng Zhan 2.1 Introduction 21 2.2 Anti-HIV Agents 22 2.2.1 Terpenes 23 2.2.2 Phenylpropanoids 24 2.2.3 Anthraquinones 25 2.2.4 Alkaloids 26 2.3 Natural Alkaloids With Activity Against HBV and HCV Infections 26 2.4 Anti-Influenza Virus Agents 28 2.5 Natural Products Active Against Herpesviruses 30 2.6 Natural Products Against Chikungunya Virus 31 2.7 Natural Products Targeting Dengue Virus 32 2.8 Natural Products Targeting Coronaviruses 33 2.9 Natural Products Against Other Viral Infections 36 2.10 Conclusion 37 Acknowledgements 37 References 37 3 Bioactive Component of Black Pepper-Piperine: Structure-Activity Relationship and Its Broad-Spectrum Activity—An Overview 43 Arthi Sivashanmugam and Sivan Velmathi List of Abbreviations 44 3.1 Introduction: What is a Natural Product? 44 3.2 Black Pepper 48 3.2.1 Constituents of Black Pepper 51 3.2.2 Major Alkaloids of Black Pepper 51 3.3 Piperine—Active Molecule of Pepper 52 3.3.1 Isolation of Piperine 52 3.3.2 Piperine as Potential Drug 54 3.3.2.1 Metabolism of Piperine 54 3.3.2.2 Structure-Activity Relationship 55 3.3.2.3 Piperine and Piperine Analogs 59 3.3.2.4 Synergistic Activity of Piperine 72 3.4 Overall Summary and Conclusion 88 References 89 4 Chemoenzymatic Synthesis of Pharmacologically Active Compounds Containing Chiral 1,2-Amino Alcohol Moiety 93 Pankaj Gupta and Neha Mahajan 4.1 Introduction 94 4.1.1 Chirality 94 4.1.2 Biocatalysis 96 4.1.2.1 Biocatalysis is Green and Sustainable 97 4.1.2.2 Industrial Applications of Biocatalysts 98 4.1.3 Vicinal Amino Alcohols 99 4.2 Synthetic Approaches Toward 1,2-Amino Alcohols 102 4.2.1 Chemoenzymatic Synthesis of L-Norephedrine 102 4.2.2 Synthesis of Valinol 106 4.2.3 Chemoenzymatic Synthesis of Atazanavir 107 4.2.4 Chemoenzymatic Synthesis of Levamisole 107 4.2.5 Chemoenzymatic Synthesis of Optically Active (R)- and (S)-Aryloxypropanolamines 108 4.2.6 Chemoenzymatic Preparation of Trans-(1R,2R)-and Cis (1S,2R)-1-Amino-2-Indanol 112 4.2.7 Synthesis of Enantiomerically Pure 2-Aminopentane-1,3-Diol and 2-Amino-1,3,4-Butanetriol (ABT) 113 4.2.8 Synthesis of Optically Active Cytoxazone 115 4.2.9 Chemoenzymatic and Highly Integrated Synthesis of (S)-Tembamide 116 4.2.10 Chemoenzymatic Synthesis of Paclitaxel C13 Side Chain 117 4.3 Conclusion 118 Acknowledgements 119 References 119 5 1,4-Naphthoquinone: A Privileged Structural Framework in Drug Discovery 133 Umar Ali Dar, Mehnaz Kamal and Shakeel A. Shah 5.1 Introduction 133 5.1.1 Overview 134 5.2 Various Targets of 1,4-Naphthoquinone for Its Actions 135 5.2.1 Bacterial Topoisomerase II-DNA Gyrase for Antibacterial Action 135 5.2.2 Mammalian Topoisomerases I and II for Antitumor Action 135 5.2.3 HIV-1 Integrase and Proteinase for or Antiviral Action 135 5.2.4 Dihydroorotate Dehydrogenase for Antimalarial Action 136 5.2.5 Trypanothione and Trypanothione Reductase (TryR) for Leishmanicidal Action 137 5.2.6 Mitochondrial Cytochrome (Coenzyme Q) for Antifungal Action 137 5.3 Antifungal Activity 137 5.4 Antibacterial Activities 140 5.5 Anticancer Activity 142 5.6 Antileishmanial Activity 145 5.7 Antimalarial Activity 147 5.8 Antiviral Activity 149 5.9 Conclusion 149 Acknowledgments 150 References 150 6 Design and Synthesis of Spirobiisoxazoline Derivatives 155 K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali 6.1 Introduction 155 6.2 Literature Review on Spiroisoxazolines 157 6.2.1 Chemistry 157 6.2.2 Previous Approaches 159 6.2.3 Biological Importance 163 6.3 Literature Review on Quinones 166 6.3.1 Chemistry 166 6.3.2 Synthetic Approach 167 6.3.3 Biological Importance 169 6.4 Review on 1,3 Dipolar Cycloadditions of Oxime Chloride With Allenoates 171 6.5 Present Work; Spirobiisoxazoline 172 6.5.1 Results and Discussion 172 6.5.1.1 Synthetic Studies 172 6.5.1.2 Spectral Analysis 176 6.5.2 Experimental Section 178 6.6 Conclusion 179 References 179 7 Potential of Metal Complexes for the Treatment of Cancer: Current Update and Future Prospective 183 Shipra Yadav 7.1 Introduction 184 7.2 Conclusion and Future Prospective 195 References 196 8 Design, Synthesis, and Biological Evaluation of Aziridynyl Quinone Derivatives 205 K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali 8.1 Introduction 206 8.2 Aziridines 207 8.2.1 Literature Review 207 8.2.2 Synthetic Approach 208 8.2.3 Biological Importance 209 8.3 Quinones 211 8.3.1 Literature Review 211 8.3.2 Synthetic Approach 213 8.3.3 Biological Importance 215 8.4 Aziridinyl Quinone Derivatives 217 8.4.1 Present Work 219 8.4.2 Synthetic Studies 220 8.4.2.1 Confirmation of Regioisomers 63 and 63a 223 8.4.2.2 Confirmation of Regioselectivity for Diaziridinyl Compounds 227 8.4.3 Biological Evaluation 228 8.4.3.1 Antibacterial Activity 229 8.4.3.2 Minimum Bactericidal Concentration 230 8.4.3.3 Biofilm Inhibition Assay 233 8.4.3.4 Antifungal Activity 235 8.4.3.5 Minimum Fungicidal Concentration 237 8.4.3.6 Cytotoxic Activity 237 8.4.4 Experimental Section 241 8.4.4.1 Chemistry 241 8.4.4.2 Biological Studies 243 8.5 Conclusion 246 References 247 9 Exploring the Promising Anticancer and Antimicrobial Potential of Bioactive Triazoles and Their Related Compounds 251 Manzoor Ahmad Malik, Ovas Ahmad Dar, Nitu Singh, Gulshitab Aalam and Athar Adil Hashmi 9.1 Introduction 252 9.2 Anticancer Triazole Derivatives 256 9.3 Antimicrobial Triazole Derivatives 267 9.4 Conclusion 275 References 276 10 Fused Triazolo Isoquinoline Derivatives—Design, Synthesis, and Biological Evaluation 281 K. Jones Madhuswapnaja, Satyanarayana Yennam and Murthy Chavali 10.1 Introduction 282 10.2 Literature Review on 1,2,4 Triazoles 283 10.2.1 Chemistry 283 10.2.2 Synthetic Approach 284 10.2.3 Biological Importance 287 10.3 Review on Isoquinoline and Fused Triazolo Isoquinolines 292 10.4 Present Work 294 10.5 Results and Discussion 294 10.5.1 Synthetic Studies 294 10.5.1.1 Confirmation of Regioisomer 298 10.5.2 Spectral Analysis 299 10.5.2.1 1H NMR Spectral and Mass Analysis 299 10.5.2.2 13C NMR Spectral Analysis 299 10.5.3 Biological Studies 299 10.5.3.1 Antifungal Activity 300 10.5.3.2 Minimum Fungicidal Concentration 300 10.5.3.3 Ergosterol Biosynthesis Inhibition 303 10.5.3.4 Cytotoxic Activity 305 10.5.4 Molecular Docking Studies 305 10.5.5 Experimental Section 309 10.5.5.1 Chemistry 309 10.5.5.2 Biological Studies 311 10.5.6 Molecular Modeling Procedure 314 10.6 Conclusion 314 References 315 11 Amide as a Potential Pharmacophore for Drug Designing of Novel Anticonvulsant Compounds 319 Mehnaz Kamal, Talha Jawaid, Umar Ali Dar and Shakeel A. Shah 11.1 Introduction 320 11.2 Chemistry of Amides 321 11.2.1 Synthesized Methods Utilized for Amide Bond Formation 321 11.2.2 Amide Pharmacophore Containing Anticonvulsant Drug 322 11.2.3 Anticonvulsant Activity 322 11.3 Conclusion 337 Acknowledgments 337 References 337 12 Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide as Biologically Important Signaling Molecules With the Significance of Their Respective Donors in Ophthalmic Diseases 343 R. C. Maurya and J. M. Mir 12.1 Introduction 344 12.2 A Meaningful Introduction to Gasotransmitters 346 12.3 Biosynthesis and Target of NO, CO, and H2S 347 12.3.1 Biological Synthesis and Target of NO 347 12.3.2 Biological Production and Target of CO 349 12.3.3 Biosynthesis and Target Sites of H2S 353 12.4 Gasotransmitters in the Mission of Vision (Eye-Health Contribution) 357 12.4.1 NO News is Good News for Eyes: NO Donors for the Treatment of Eye Diseases 357 12.4.1.1 Nitric Oxide Releasing Molecules (NORMS) and the IOP 359 12.4.2 Carbon Monoxide, CORMS, and the Ocular System 363 12.4.3 Hydrogen Sulfide and Ophthalmic Diseases 367 12.5 Concluding Remarks and Future Outlook 368 References 368 13 Influence of rol Genes for Enhanced Biosynthesis of Potent Natural Products 379 Erum Dilshad, Huma Noor, Nabgha Nosheen, Syeda Rehab Gilani, Umar Ali and Mubarak Ali Khan 13.1 Introduction 380 13.2 Secondary Metabolites or Natural Products 381 13.2.1 Classes of Natural Products (Secondary Metabolites) 382 13.2.1.1 Terpenoids 382 13.2.1.2 Phenolic Compounds 383 13.2.1.3 Alkaloids 383 13.2.2 Strategies to Enhance Natural Products 383 13.2.2.1 Plant Cell Culture (Somaclonal Variation) 384 13.2.2.2 Genetic Transformation of Plant Cell 384 13.2.2.3 Multiple Gene Transfer Through Improving Vectors 385 13.2.3 Genetic Engineering/Metabolic Engineering 385 13.3 rol Genes 386 13.3.1 Origin of rol Genes 387 13.3.2 Types of rol Genes 388 13.3.2.1 The rolA Gene 388 13.3.2.2 The rolB Gene 389 13.3.2.3 The rolC Gene 390 13.3.2.4 The rolD Gene 391 13.3.3 The Combined Effect of Genes rol on Secondary Metabolism 392 13.4 Mechanism of Action of rol Genes 393 13.4.1 How rol Genes Regulate ROS Production and Mediate Secondary Metabolites Production 393 13.4.1.1 Agrobacterium (rol Gene) and ROS 393 13.4.1.2 Plants Secondary Metabolism and ROS 394 13.4.1.3 Stabilization of Secondary Metabolites Biosynthesis Through rol Genes 395 13.5 Impact of rol Gene on Different Secondary Metabolites 395 13.5.1 Impact of rol Gene on Alkaliods 395 13.5.2 Impact of rol Genes on Flavonoids 396 13.5.3 Impact of rol Genes on Terpenoids 396 13.6 Conclusion 397 References 397 Index 405