Flavonoids and Phenolics (Medicinal Chemistry Lessons From Nature, Volume 1)

Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases. This book explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, molecular modelling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice. Each chapter follows a specific format for a phytochemical agent with common chemical features: • General background on the (phyto)chemistry of the scaffold • General background on the pharmacological profile of the scaffold • A Description of the proposed derivatives and their advantages with respect to the parent compounds (emphasizing the synthetic approaches and structure-activity relationships) • In silico analysis of the crucial interactions with the biological target • Clinical studies and patent survey (if available) on the new and proposed structures The objective of this book set is to fulfil gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians. Cover Title Copyright End User License Agreement Contents Foreword KEY FEATURES Preface List of Contributors Polyphenols and Flavonoids: Chemical, Pharmacological and Therapeutic Aspects Stefania Cesa1,*, Francesco Cairone1 and Celeste De Monte1 INTRODUCTION CHEMICAL STRUCTURES, CLASSIFICATION AND PROPERTIES OF FLAVONOIDS Classes of Flavonoids with the B Ring on C2 Classes of Flavonoids with the B Ring on C3 Classes of Flavonoids Where the B Ring is Connected to the C Ring Through the 4th Position Classes of Open-Chain Flavonoids PHARMACOLOGICAL ASPECTS OF POLYPHENOLS AND FLAVONOIDS BIOAVAILABILITY AND METABOLISM OF FLAVONOIDS, TOXICOLOGICAL ACTIVITY AND SEMI-SYNTHETIC STRATEGIES ADME of Flavonoids Factors that Could Affect ADME of Flavonoids Toxicity of Flavonoids Strategies for a Better Investigation of Flavonoids Properties CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Recent Development of Hybrids and Derivatives of Resveratrol in Neurodegenerative Diseases Barbara De Filippis1,* and Marialuigia Fantacuzzi1 INTRODUCTION MULTITARGET ANALOGUES OF RSV Hybrids of RSV Derivatives of RSV Schiff Base Derivatives of RSV CONCLUDING REMARKS ABBREVIATIONS: CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Biological Activities of Synthetic Derivatives of Xanthones: An Update (2016-2020) Cristina Scarpecci1 and Sara Consalvi1,* INTRODUCTION XANTHONE SYNTHETIC DERIVATIVES FOR CANCER THERAPY Caged Xanthones (CXs) Mangostin Analogs Carboxyxanthones Dihydroxyxanthones N-Xanthone Benzensulphonamides Dioxygenated Xanthones Xanthones Bearing Long Side Chains ANTIBACTERIAL XANTHONE SYNTHETIC DERIVATIVES Amphiphilic Xanthones Amino Acid-Conjugated Xanthones Miscellaneous Compounds ANTIFUNGAL XANTHONE SYNTHETIC DERIVATIVES ANTIMALARIAL XANTHONE SYNTHETIC DERIVATIVES XANTHONE SYNTHETIC DERIVATIVES AS ANTI-INFLAMMATORY AGENTS ANTI-ALZHEIMER XANTHONE SYNTHETIC DERIVATIVES XANTHONE SYNTHETIC DERIVATIVES AS Α-GLUCOSIDASE INHIBITORS CONCLUDING REMARKS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES Combretastatin Derivatives as Tubulin Inhibitors: A Fascinating Journey from Nature to Drug Discovery Strategies Alessandra Ammazzalorso1,* and Trond Vidar Hansen2 INTRODUCTION INSIGHTS ON MECHANISM OF ACTION OF COMBRETASTATINS Development of Combretastatin Prodrugs Fosbretabulin, Ombrabulin and Oxi4503 Combretastatin Prodrugs With Improved Drug Delivery Ability Bioreductive Prodrugs of Combretastatins Photoresponsive Hybrid Prodrugs of Combretastatins DEVELOPMENT OF COMBRETASTATIN DERIVATIVES Combretastatin Derivatives Obtained by Bridge Modifications Carbocyclic Derivatives Heterocyclic Derivatives RECENT ADVANCES IN DRUG DELIVERY SYSTEMS OF COMBRETASTATIN CONCLUDING REMARKS ABBREVIATIONS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES Natural Flavonoid and Chalcone Scaffolds as Leads for Synthetic Antitubercular Agents Federico Appetecchia1, Mariangela Biava1 and Giovanna Poce1,* INTRODUCTION FLAVONOIDS Chalcones Simple-substituted Chalcones Heteroaryl and Hybrid Chalcones CONCLUDING REMARKS CONSENT OF PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGMENT REFERENCES In Silico Approaches to Naturally Existing Chalcones and Flavonoids on Mao Inhibitory Action: A Boon to CNS Drug Discovery Arafa Musa1,2, Della Grace Thomas Parambi3, Mutairah Shaker Alshammari4, Rania Bakr3, Mohammed A. Abdelgawad3,5, Dibya Sundar Panda6, Manoj Kumar Sachidanandan7, Vaishnav Bhaskar8, Leena K. Pappachen8 and Bijo Mathew8,* INTRODUCTION CHALCONES Prenylated Chalcone: Xanthoangelol and 4-Hydroxyderricin Resveratrol Dihydrochalcones Flavonoids Quercetin Xanthones Homoisoflavonoids Thioflavones Sideritis Flavonoids Studies on Apigenin, Kaempferol, Quercetin and Luteolin PRENYLAPIGENIN Bavachinin and Bavachin Genistein Phytochemicals from Clitoria Ternatea O-Methylated Flavonoids CONCLUDING REMARKS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Lignins and Lignans – Recent Developments and Trends Regarding their Pharmaceutical Properties Luc Zongo1 and Heiko Lange2,* INTRODUCTION LIGNIN Biosynthesis and Structural Features of Lignins Isolation of Lignins Lignin Fractionation LIGNANS Biosynthesis and Structural Features of Lignans ANALYTICAL TOOLS FOR ANALYSES OF LIGNINS AND LIGNANS Fourier-Transform Infrared Spectroscopy and Raman Spectroscopy NMR Spectroscopy-Based Analysis Methods Size Exclusion and Gel Permeation Chromatographic Methods Mass Spectrometry Methods Anti-Oxidant Activity Assays LIGNINS FOR USE IN PHARMACEUTICAL AREA Lignin as Source of Pharmaceutical Activity LIGNIN AS MATERIAL FOR MICRO- AND NANOSTRUCTURES FOR PHARMACEUTICAL USE Lignin-Containing Film Preparations for Pharmaceutical Applications NANOPARTICLES Micro- and Nanoscaled Core-shell Structures Incorporation of Actives in Lignin Particle and Lignin Capsule Structures Entrapment Vs. Encapsulation Vs. Adsorption Covalent and Electrostatic Surface Functionalisation PHARMACEUTICAL PROPERTIES OF LIGNANS Dietary Value of Lignans in Health Promotion Antiaging Potential of Lignans Anti-Inflammatory Properties of Lignans Anticancer Properties of Lignans Antibiotic Properties of Lignans Antiviral Properties of Lignans Hepatoprotective Effects of Lignans The Neuroprotective Effects of Lignans The Physicochemical Properties of Lignans in Drug Design CONCLUDING REMARKS AND FUTURE PERSPECTIVES CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES Semisynthetic Resveratrol-derived Systems: A Synergism between Nature and Organic Synthesis Antonella Capperucci1 and Damiano Tanini1,* INTRODUCTION RESVERATROL ETHERS AND RELATED DERIVATIVES Resveratryl Esters and Related Derivatives Selenium-containing Resveratrol Derivatives Resveratrol-Derived Hybrids and Other Conjugates CONCLUSION CONFLICT OF INTEREST ACKNOWLEDGEMENT CONSENT OF PUBLICATION REFERENCES Aurone Scaffold and Structural Analogues for the Development of Monoamine Oxidase (MAO) Inhibitors Paolo Guglielmi1, Virginia Pontecorvi1,* and Atilla Akdemir2 INTRODUCTION AURONES AND THEIR STRUCTURAL-RELATED COMPOUNDS Aurones Indanone and Tetralone Derivatives Homoisoflavonoids Derivatives (3-Benzylidenechroman-4-ones) CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES Coumarins as Carbonic Anhydrase Inhibitors Claudiu T. Supuran1,* CARBONIC ANHYDRASE INHIBITORS AND ACTIVATORS COUMARINS WITH CA INHIBITORY ACTION Natural Product Coumarins Synthetic Coumarins Other Drug Design Studies using Coumarins as Lead Molecules CONCLUSIONS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Phenols and Polyphenols as Carbonic Anhydrase Inhibitors Alessandro Bonardi1, Claudiu T. Supuran1 and Alessio Nocentini1,* PHENOLS AND POLYPHENOLS Carbonic Anhydrases CA Inhibition Mechanism of Phenol Derivatives Phenolic Derivatives Inhibit Human CAs Synthetic/Semisynthetic Phenolic Derivatives as Hcas Inhibitors Natural and Synthetic/Semisynthetic Phenols Inhibit Carbonic Anhydrases From Bacteria, Fungi, Protozoa, And Diatoms In Silico Studies of the Binding Mode of Phenolic Derivatives to CA Isoforms CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES The Role of Flavonoids and other Selected (Poly) Phenols in Cancer Prevention and Therapy: A Focus on Epigenetics Melissa D’Ascenzio1,* INTRODUCTION Chemoprevention and the Epigenetic Mechanisms Associated with Chronic Diseases EPIGENETIC MARKS AND EPIGENETIC PROTEINS DNA Methyltransferases Histone Acetyl Transferases (Hats) and Histone Deacetylases (Hdacs) Histone Methyl Transferases (Hmts) Other Post-Translational Modifications FLAVONOIDS AS EPIGENETIC MODULATORS IN CHEMOPREVEN-TION AND CANCER THERAPY FLAVONOLS, FLAVONES, ISOFLAVONES, AND ANTHOCYANINS Flavonols: Quercetin and Kaempferol Flavones: Apigenin, Luteolin and Chrysin Isoflavones: Genistein and Daidzein Anthocyanins Flavanols: Catechins from Green Tea CURCUMIN AND CURCUMINOIDS RESVERATROL AND OTHER STILBENE DERIVATIVES CONCLUDING REMARKS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Subject Index Back Cover Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases. This book explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, and molecular modeling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice. Each chapter follows a specific format for a phytochemical agent with common chemical features: bull; General background on the (phyto)chemistry of the scaffold bull; General background on the pharmacological profile of the scaffold bull; A Description of the proposed derivatives and their advantages with respect to the parent compounds (emphasizing the synthetic approaches and structure-activity relationships) bull; In silico analysis of the crucial interactions with the biological target bull; Clinical studies and patent survey (if available) on the new and proposed structures The objective of this book set is to fulfil gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians.