Multiple Action-Based Design Approaches to Antibacterials

Preface
Contents
About the Author
1 Antibacterials
	1.1 Bacteria
	1.2 Antibacterial Action
	1.3 Bacterial Resistance to Antibacterials
		1.3.1 Introduction to Key Resistance Mechanisms
		1.3.2 Resistance and Resilience
		1.3.3 The Gram-Negative Challenge
		1.3.4 Other Survival Strategies
	1.4 Approaches to Meeting Needs
	1.5 Ways to Achieve Multi-action Effects
	1.6 Bacterial Over Host Selectivity
	References
2 Antibacterial Combinations
	2.1 Introduction
		2.1.1 Dual Combinations Resulting in Two Actions
		2.1.2 Dual Combinations Resulting in Three or More Actions
		2.1.3 Triple Combinations Resulting in Three or More Actions
		2.1.4 Quadruple Combinations with Four or More Actions
		2.1.5 Pentuple Combinations
	2.2 Summary
	References
3 Single Molecule Non-cleavable Multiply Active Antibacterials
	3.1 Introduction to General Design Considerations
		3.1.1 General Approaches to Hybrids
		3.1.2 Factors in Antibacterial Hybrid Design
	3.2 Designing for Mainly Dual Activity
		3.2.1 Dual Action Antibacterial Hybrids
		3.2.2 Examples of Dual Action Agents from Nature
		3.2.3 Berberine as a Starting Point for Design
	3.3 Triple Action Antibacterial Hybrid Agents
		3.3.1 General Points
		3.3.2 Potential Design Based on Pharmacophoric Elements
		3.3.3 Established and Potential Single Molecule Triple Action or Interaction Agents
		3.3.4 Designing Potential New Non-cleavable Triple Action Agents
	3.4 More Than Triple Action Hybrid Agents
	References
4 Design Principles and Development of Prodrugs for Multiply Active Antibacterials
	4.1 Definitions
		4.1.1 Carrier-Linked Prodrugs (Carrier Prodrugs)
		4.1.2 Bioprecursor Prodrugs
	4.2 Introduction to Prodrugs for Triple or Higher Action Antibacterials
		4.2.1 Design Considerations
		4.2.2 Classification and Examples of Cleavable Types for Triple or Higher Action
		4.2.3 Cleavable Type I
		4.2.4 Cleavable Type II
		4.2.5 Cleavable Type III
		4.2.6 Cleavable Type IV
	4.3 Release Mechanisms and Prodrug Design
		4.3.1 Biological
		4.3.2 Chemical
		4.3.3 Physical
	4.4 Metabolism Activated Multi-targeting
	4.5 Conclusion
	References
5 Future Possibilities
	5.1 Introduction
	5.2 New Combinations and Single Molecules with Multi-activity Development Potential
		5.2.1 Combinations
		5.2.2 Hybrid Molecule Possibibilities
	5.3 Search for Different Chemical Structure Types
		5.3.1 In Silico Advances
	5.4 New Modes of Action/New Targets
	5.5 DNA and RNA Level Modulation
	5.6 Proteins and Antibacterials
	5.7 Concluding Remarks
	References
Index