Frontiers in Drug Design and Discovery is a book series devoted to publishing the latest and the most important advances in drug design and discovery. Eminent scientists have contributed chapters focused on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships.
This book series should prove to be of interest to all pharmaceutical scientists who are involved in research in drug design and discovery and who wish to keep abreast of rapid and important developments in the field.
Volume 12 of this series brings together reviews covering homology modeling and anti-infective drug discovery.
Topics included in this volume are:
- Homology Modelling: A Computational Tool in Drug Design and Discovery
- Anti-trypanosomatid Drugs/Candidates in Clinical Trials: What's New and What's Missing?
- Nitroheterocyclics As Anti-Tuberculosis Agents: An Overview
- SARS-CoV-2 Protease Inhibitors of Natural Origin: Current Scenario and Future Prospects as Anti-COVID-19 Agents
Readership
Pharmaceutical scientists, biochemists, researchers in medicine and public health projects
Table of Contents
CONTENTS
PREFACE
LIST OF CONTRIBUTORS
CHAPTER 1 HOMOLOGY MODELLING: A COMPUTATIONAL TOOL IN DRUG DESIGN AND DISCOVERY
- Shivangi Agarwal, Ekta Verma and Sushil K. Kashaw
INTRODUCTION TO HOMOLOGY MODELLING
SEQUENCE ALIGNMENT
- Based on Length of Sequence
- Global Alignment
- Local Alignment
- Based on Number of Sequence
- Pairwise Sequence Alignment
- Multiple Sequence Alignment (MSA)
DATABASE SIMILARITY SEARCHING FASTA
- Working of FASTA Algorithm
BLAST (Basic Local Alignment Search Tool)
BASICS STEPS IN HOMOLOGY MODELING
- Searching for Query Sequence
- Template Selection
- Alignment of Query Sequence with Template
- Model Building
- Loop Modeling
- Modeling of a Loop
- Model Validation
- Ramachandran Plot
- Errat Plot
- ProsaII folding Energy Analysis
- G-factor
- Verify 3D
- Z-Score
- RMSD Analysis
APPLICATION OF HOMOLOGY MODELLING
CONCLUSION
ACKNOWLEDGEMENT
REFERENCES
CHAPTER 2 ANTI-TRYPANOSOMATID DRUGS/CANDIDATES IN CLINICAL TRIALS: WHAT'S NEW AND WHAT'S MISSING?
- Marcieli Fabris, Kaio Maciel de Santiago-Silva, Camilo Henrique da Silva Lima
- Marcelle de Lima Ferreira Bispo and Priscila Goes Camargo
INTRODUCTION
- Human African Trypanosomiasis (HAT)
- Chagas Disease (CD)
- Leishmaniasis
CURRENTLY USED THERAPEUTIC AGENTS
- Benznidazole
- Fexinidazole
- Nifurtimox
- Meglumine Antimoniate
- Intralesional Therapy
- Miltefosine
- Paromomycin
- Pentoxifylline
AZOLE ANTIFUNGAL
- Fosravuconazole L-lysine ethanolate, Posaconazole and Ravuconazole (E1224)
BENZOXABOROLES: ACOZIBOROLE (SCYX-7158) AND DNDI-6148
NITROAROMATIC COMPOUNDS: DNDI-0690
NITROGEN HETEROCYCLES
- GSK3186899/DDD853651
- Novartis LXE408 and GSK3494245/DDD1305143
MISCELLANEOUS AGENTS
- 18-Methoxycoronaridine
- Colchicine
CONCLUSION
ACKNOWLEDGEMENT
REFERENCES
CHAPTER 3 NITROHETEROCYCLICS AS ANTI-TUBERCULOSIS AGENTS: AN OVERVIEW
- Suparna S. De, Shweta D. Gupta and Mariam S. Degani
INTRODUCTION
NITRO AROMATIC/HETEROAROMATIC CHEMISTRY
- Electronic Properties of the Nitroarenes
- Geometry and Spectral Characteristics of Nitroarenes
- Nitro-moiety: the Toxicophore
- Experimental Tests to check Genotoxicity
- Strategies to Reduce Toxicity of Nitro Heteroaromatic Compounds
NITROHETEROCYCLIC COMPOUNDS AS ANTI-TB AGENTS
- Nitroimidazoles -Delamanid and Pretomanid
- Introduction and History
- Mechanism of Action
- Mechanism of Resistance
- Structure Activity Relationship (SAR)
- Pharmacokinetic Properties (ADMET)
- Nitro-benzothiazinones -BTZ043 and Macozinone
- Introduction and History
- Mechanism of Action
- Mechanism of Resistance
- SAR
- Pharmacokinetic Properties (ADMET)
- Nitrothiazole -Nitazoxanide
- Introduction and History
- Mechanism of Action
- Disruption of Membrane Potential and pH Homeostasis
- Autophagy
- Cytoplasmic RNA Sensor Pathways Re-activation
- Mechanism of Resistance
- SAR
- Pharmacokinetic Properties (ADMET)
- Other Nitro Heterocyclic Classes
- Nitrothienopyrimidines
- Nitrobenzenes
- 5-membered Nitro-heteroaromatic Compounds
- Nitrothiophenes
- Nitrotriazoles
CONCLUSION AND FUTURE PERSPECTIVES
ACKNOWLEDGEMENTS
REFERENCES
CHAPTER 4 SARS-COV-2 PROTEASE INHIBITORS OF NATURAL ORIGIN: CURRENT SCENARIO AND FUTURE PROSPECTS AS ANTI-COVID-19 AGENTS
- Naveen Kumar Reddy, A. Srinivasa Rao, D. Geetha Mounika, Katharigatta N. Venugopala
- Pobitra Borah, Pran Kishore Deb and M. Raghu Prasad
INTRODUCTION
SECONDARY METABOLITES ON SARS-COV-2 MPRO
- Alkaloids
- Terpenoids
- Flavonoids
- Tannins
- Polyphenols
- Lignans
- Glycosides
LICHEN COMPOUNDS ON SARS-COV-2 MPRO
MICROBIAL NATURAL PRODUCTS ON SARS-COV-2 MPRO
MARINE SOURCES ON SARS-COV-2 MPRO
MISCELLANEOUS NATURAL PRODUCTS ON SARS-COV-2 MPRO
CONCLUSION
LIST OF ABBREVIATIONS
REFERENCES
SUBJECT INDEX
Author
- M. Iqbal Choudhary
