Old and New Strategies for the Discovery of Antibacterial Agents

Abstract

In this review we have tried to present a complete and integrated picture of the old and new ways to discover antibacterial agents. The development of new antibacterial agents can be made from derivatives of known antibacterial agents or by identification of novel agents active against previously unexploited targets. The genetic and biochemical basis of resistance to most classes of antibacterial agents is now known and this has been important in the design of a rational strategy that can be used to counteract resistance. This strategy can follow two approaches: i. Modification of the basic structure of the antibacterial agent, which circumvents antibacterial resistant mechanisms, and ii. Development of a compound inhibiting the mechanism of resistance for an antibacterial agent, hence the concomitant administration of the antibacterial agent plus the inhibitor, as a co-drug, will potentiate this activity. There are also two main approaches to find new protein targets: 1. Classical and, 2. Genomic. The first includes the study of secondary metabolites of bacteria and fungi with antibacterial activity, and it has now been expanded to include plant extracts and marine macro-and microorganisms, as well as non-cultivable soil bacteria. Recent tools such as comparative genomic, combinatorial chemistry, and computerized modelling have helped in the development of new antibacterial agents. Finally, other approaches, such as bacteriophages, antisense RNA and proteins involved in pathogenicity to find new antibacterial drugs are currently investigated.

In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii

“…Two approaches can be used to find new antibacterial agents. The first is to improve an existing antimicrobial agent by changing its structure and thereby increasing its activity or circumventing the mechanism of resistance, and the second is to find a completely new antimicrobial agent with a new protein or molecular target [19]. The objective of this study was to investigate the activity of 15 peptides against colistin‐susceptible and colistin‐resistant A. baumannii .…”

2D-QSAR Study of Indolylpyrimidines Derivative as Antibacterial against Pseudomonas aeruginosa and Staphylococcus aureus: A Comparative Approach

“…Many chemical entities work as antibacterial agents by inhibiting the DNA synthesis of cell wall by blocking the enzymes such as DNA gyrase and dihydrofolate reductase and even inhibiting enzymes processing the development of peptidoglycan layer [4,5].…”

Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria

“…The development of new antibiotics can be achieved from derivatives of known antimicrobial agents or by identification of novel agents active against previously unexploited targets [12]. The former procedure is mainly based on the knowledge of the mechanisms of resistance and the derivatives are designed to avoid these mechanisms.…”