Computer-Aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates

Preface
Acknowledgments
Authors

Chapter 1 ◾ Lipopeptides and Computer-Aided Drug Design
1.1 What are Lipopeptides
1.2 Advantages and Applications of Lipopeptides
1.2.1 Biomedical and Therapeutic Applications of Lipopeptides 
1.2.2 Cyclic Lipopeptides: Potent Mosquito Larvicidal Agents 
1.2.3 Antiparasitic Activity of Lipopeptides 
1.2.4 Antiviral Activity of Lipopeptides 
1.2.5 Antitumor Activity and Lipopeptides-Induced Apoptotic Pathway 
1.2.6 Anti-Obesity Activity of Lipopeptides 
1.2.7 Thrombolytic Activity of Lipopeptides 
1.3 Computer-Aided Drug Designing (In Silico Design) 
1.3.1 Homology Modeling (HM) 
1.3.2 Molecular Docking Simulations (MDS) 
1.3.3 Study of QSAR 
1.3.4 Pharmacokinetics/ADMET Study 
1.3.4.1 Absorption/Administration (Pharmacokinetics)
1.3.4.2 Distribution (Pharmacology)/Dispersion or Dissemination of Substances
1.3.4.3 Metabolism 
1.3.4.4 Excretion of the Drug 
1.3.4.5 Toxicity 
1.3.5 Pharmacophore Properties 
1.4 Pharmacophore Study as Application for Drug-Related Activities
1.5 CONCLUSIONS
REFERENCES 
Chapter 2 ◾ Pore-Forming Antibacterial Lipopeptides
2.1 INTRODUCTION
2.2 FRIULIMICIN B 
2.2.1 Activity of Friulimicin B in Bacterial Cell 
2.2.2 Ligands of Friulimicin B 
2.2.3 Docking Studies for Friulimicin
2.2.4 ADMET Study for Friulimicin 
2.2.5 Pharmacophore Study for Friulimicin
2.3 TRIDECAPTIN A 
2.3.1 Structure of Tridecaptin A 
2.3.2 Mode of Action of Tridecaptin A
2.3.3 Ligands of Tridecaptin A 
2.3.4 Molecular Docking Studies of Tridecaptin
2.3.5 ADMET Properties 
2.3.6 Concept of Pharmacophore for Tridecaptin A 
2.4 TSUSHIMYCIN 
2.4.1 Introduction of Tsushimycin 
2.4.2 Physiological Effect of Tsushimycin 
2.4.3 Identification of Ligands of Tsushimycin 
2.4.4 Molecular Docking Simulations 
2.4.5 ADMET Properties of Tsushimycin 
2.4.6 Pharmacophore Studies of Tsushimycin with its Ligands 
2.5 SUMMARY 
REFERENCES 

Chapter 3 ◾ Antibacterial Lipopeptides 
3.1 POLYMYXIN AS AN ANTIMICROBIAL DRUG 
3.1.1 Biosynthesis 
3.1.2 Antibacterial Activity of Polymyxin 
3.1.3 Identification of Drug Target Sites 
3.1.4 Ligand-Based Molecular Docking 
3.1.5 Drug Behavior Analysis Using ADMET 
3.1.6 Pharmacophore Models for Polymyxin 
3.2 LASPARTOMYCIN 
3.2.1 Antimicrobial Activity of Laspartomycin 
3.2.2 Ligands of Laspartomycin 
3.2.3 Molecular Docking as a Tool for Drug Discovery 
3.2.4 ADMET Properties of Laspartomycin 
3.2.5 Pharmacophore Modeling of Laspartomycin 
3.3 VANCOMYCIN 
3.3.1 Biosynthesis of Vancomycin 
3.3.2 Action of Vancomycin against Bacteria 
3.3.3 Ligand Identification of Vancomycin 
3.3.4 Studies on Molecular Docking of Vancomycin 
3.3.5 ADMET Studies of Vancomycin 
3.3.6 Ligand-Based Pharmacophore Modeling of Vancomycin 
3.4 SUMMARY 
REFERENCES 

Chapter 4 ◾ Antifungal Lipopeptides 
4.1 INTRODUCTION 
4.2 FENGYCIN 
4.2.1 Introduction 
4.2.2 Antifungal Properties of Fengycin 
4.2.3 Identification of Ligands 
4.2.4 Molecular Docking for Drug Targeting 
4.2.5 ADMET Studies of Fengycin 
4.2.6 Pharmacophore Tool for Drug Discovery 
4.3 ITURIN A 
4.3.1 Introduction 
4.3.2 Mechanism of Action of Iturin A 
4.3.3 Ligand of Iturin A 
4.3.4 Drug–Ligand Interaction by Molecular Docking 
4.3.5 ADMET Modeling of Iturin A 
4.3.6 Pharmacophore Modeling of Iturin A 
4.4 SURFACTIN 
4.4.1 Introduction 
4.4.2 Mode of Action – Surfactin 
4.4.3 Discovering Ligands of Surfactin 
4.4.4 Molecular Docking as a Tool for Design of Drugs 
4.4.5 ADMET Studies of Surfactin 
4.4.6 Pharmacophore Studies in Drug Design 
4.5 SUMMARY 
REFERENCES 

Chapter 5 ◾ Precursors of Lipopeptides 
5.1 PLIPASTATIN SYNTHASE 
5.1.1 Introduction 
5.1.2 Mechanism of Action of the Corresponding Lipopeptide 
5.1.3 Ligand Identification of Plipastatin Synthase 
5.1.4 Structure Determination of Plipastatin Synthase Using Homology Modeling 
5.1.5 Molecular Docking of the Generated Model
5.1.6 Pharmacokinetics of Plipastatin
5.2 FUSARICIDIN SYNTHASE
5.2.1 Introduction
5.2.2 Synthesis of Fusaricidin from Fusaricidin Synthase
5.2.3 Cytotoxic Effect of Fusaricidin Lipopeptide
5.2.4 Identification of Ligands
5.2.5 Ligand-Mediated Molecular Docking 
5.2.6 Drug Behavior Studies Using ADMET 
5.3 SUMMARY 
REFERENCES

Index