Antimicrobial Peptides and Small Molecules as Antibiotics Substitute

Abstract

Despite a century of the discovery of first natural antimicrobial peptide (AMP), lysozyme, their development as clinical candidates has not progressed successfully. AMPs are small proteins usually containing 10–50 amino acid residues, having occurrence in numerous plants, insects, amphibians, and animals. These possess a broad spectrum of activity against diverse microbes (bacteria, viruses, and fungi) finding their use as topical antiseptics, anti-inflammatory, oral mucositis, candidiasis, impetigo, chronic respiratory infection, cystic fibrosis, acute bacterial skin infections, inflammatory bowel disease, etc., clinically. More than 1200 natural peptides displaying antimicrobial potency have been isolated so far. AMPs surface in all living organisms and form the major component of the “innate” human immune system. The current antibiotic regime has already been overexploited and facing the challenge of microbial resistance. However, from past few decades, researchers and pharmaceutical companies have been focussing on the development of new and improved generations of antimicrobial agents having smaller size, more selective, more potent, more stable, broad spectrum, less toxic, cost-effective, and with easier mode of administration than the existing ones. Universally, molecules with smaller pharmacophores have often offered advantage pharmacodynamically and pharmacokinetically over their larger counterparts. A variety of small molecules displaying good antibiotic potency and a broader spectrum have been discovered, synthesized, and used therapeutically. This chapter unravels the knowledge of AMPs and novel small antibiotics, with a perspective on their synergy with currently available antibiotics, and focuses on their future prospective as therapeuticals.