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.
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
Table of Contents
Chapter 1 Preface- Iii References
- Introduction
- History Of No Field
- Diabetes-Related No Research
- Concluding Remarks
- Consent For Publication
- Conflict Of Interest
- Acknowledgement
- References
- Introduction
- Epidemiology Of Diabetes
- Diagnosis Of Diabetes
- Glucose Homeostasis
- Post-Absorptive State: The Fasting State
- Glucose Production
- Glucose Utilization
- Post-Prandial State
- Mechanisms Underlying Glucose Homeostasis
- Central Mechanisms Of Glucose Homeostasis
- Glucose Sensing By Neurons
- Peripheral Mechanisms Of Glucose Homeostasis
- Insulin
- Insulin Secretion
- Mechanism Of Insulin Secretion
- Box 1 Circulating Insulin Concentrations
- Box 2 Technical Considerations On Circulating Insulin Measurement
- Insulin Signaling Pathways
- Pathophysiology Of Type 2 Diabetes
- Insulin Resistance
- Β-Cell Dysfunction
- Concluding Remarks
- Consent For Publication
- Conflict Of Interest
- Acknowledgement
- References
- Introduction
- Role Of No In Glucose And Insulin Homeostasis
- T2D And Whole-Body No Metabolism
- No Deficiency In T2D
- T2D And Circulating No: An Epidemiologic Point Of View
- Underlying Mechanisms Of Impaired No Metabolism/Action In T2D
- Impaired L-Arginine Nos-No Pathway
- Impaired No3-No2-No Pathway
- Impaired No Transport
- Impaired No Signaling
- Concluding Remarks
- Conflict Of Interest
- Acknowledgement
- Consent Of Publication
- References
- Introduction
- Adma Biosynthesis And Metabolism
- Adma And Regulation Of No Synthesis
- Cellular Uptake Of Adma
- Inhibitory Effects Of Adma On Nos Expression And Activity
- Adma And T2D
- Ddah And T2D: Lessons From Genetic Studies
- Plasma And Tissue Concentrations Of Adma In T2D
- Plasma Adma Levels And Risk Of Diabetic Complications
- Other Methylarginines And T2D
- Pharmaceutical Interventions For Elevated Adma
- Concluding Remarks
- Conflict Of Interest
- Acknowledgement
- Consent Of Publication
- References
- Introduction
- An Overview Of Oral Microbiota
- Oral Nitrate-Reducing Bacteria
- Oral Nitrate Reduction And Nitric Oxide Homeostasis
- Changes In Oral Microbiota In T2D
- Mechanisms Linking Oral Dysbiosis With Impaired Glucose And Insulin Homeostasis
- Oral Nitrate-Reducing Bacteria And Nitric Oxide Metabolism In T2D
- Concluding Remarks
- Consent For Publication
- Conflict Of Interest
- Acknowledgements
- References
- Introduction
- A Brief Overview Of Nos Enzymes: Gene Structure And Chromosomal Localization
- Genetically-Modified Nos Enzymes And Impaired Glucose And Insulin Homeostasis
- Common Polymorphisms Of Nos Enzymes
- Common Polymorphisms Of Nnos And Inos
- Common Polymorphisms Of Enos
- The Enos Polymorphisms And Serum No Metabolites
- The Enos Polymorphisms And Development Of Insulin Resistance
- The Enos Polymorphisms And Development Of T2D
- The Enos Polymorphisms And T2D Complications
- Concluding Remarks
- Consent For Publication
- Conflict Of Interest
- Acknowledgements
- References
- Introduction
- Types Of Wound
- Pathophysiology Of Diabetic Foot Ulcer
- Peripheral Neuropathy
- Peripheral Arterial Disease (Pad)
- Phases Of Wound Healing
- Hemostasis (Coagulation)
- Inflammation
- Proliferation
- Tissue Remodeling
- Changes In Healing Phases In Diabetic Wounds
- Nitric Oxide Synthesis In The Skin
- Expression Of Nos Isoforms In The Skin
- Nos-Independent No Synthesis In The Skin
- The Role Of Surface Bacteria In Skin Production Of No
- Uva Radiation And No Production
- No And Wound Healing
- No Metabolites As An Index Of Wound No
- Role Of No Different Phases Of Wound Healing
- Inflammation
- Vasculogenesis And Angiogenesis
- Re-Epithelialization
- No And Diabetic Wound Healing
- Role Of No Different Phases Of Diabetic Wound Healing
- No And Therapeutic Strategies For Diabetic Wound
- L-Arginine
- Regulation Of Nos Expression
- Acidified Nitrite
- No Donor Systems
- Concluding Remarks
- Consent For Publication
- Conflict Of Interest
- Acknowledgement
- References
- Introduction
- Nitric Oxide And Bone: A Brief Overview
- Nos Expression In The Bone Cells
- Type 2 Diabetes And Bone Indices
- Type 2 Diabetes And Bmd
- Type 2 Diabetes And Trabecular And Cortical Bone Microarchitectures
- Type 2 Diabetes And Bone Cells
- Bone No Bioavailability In Type 2 Diabetes
- Bone Remodeling
- Bone Remodeling In Type 2 Diabetes: Role Of No
- Nitric Oxide-Based Treatment Of Diabetoporosis
- Possible Strategies For Nitric Oxide-Based Treatment Of Diabetoporosis
- Concluding Remarks
- Consent Of Publication
- Conflict Of Interest
- Acknowledgement
- References
- Introduction
- A Brief Overview Of Uric Acid Metabolism And Function
- Uric Acid Synthesis In Human: Role Of Xor
- Regulation Of Circulating Uric Acid Levels
- Physiologic Roles Of Normal Uric Acid Levels
- Pathological Effects Of Hyperuricemia
- Hyperuricemia, T2D And Insulin Resistance
- Epidemiological Evidence
- Experimental And Clinical Evidence
- Underlying Mechanisms Connecting Ua To Insulin Resistance And T2D
- Role Of No In Hyperuricemia-Induced Dysglycemia And Insulin Resistance
- Concluding Remarks
- Consent Of Publication
- Conflict Of Interest
- Acknowledgement
- References
- Introduction
- Biguanides
- General Mechanism Of Action
Author
- Simone Carradori
