Discovery and development of new antimicrobial agents

Abstract

The unprecedented growth in the number of new antibiotics over the past two decades has been the result of extensive research efforts that have exploited the growing body of knowledge describing the interactions of antibiotics with their targets in bacterial cells. Information gained from one class of antimicrobial agents has often been used to advance the development of other classes. In the case of beta-lactams, information on structure-activity relationships gleaned from penicillins and cephalosporins was rapidly applied to the cephamycins, monobactams, penems, and carbapenems in order to discover broad-spectrum agents with markedly improved potency. These efforts have led to the introduction of many new antibiotics that demonstrate outstanding clinical efficacy and improved pharmacokinetics in humans. The current review discusses those factors that have influenced the rapid proliferation of new antimicrobial agents, including the discovery of new lead structures from natural products and the impact of bacterial resistance development in the clinical setting. The development process for a new antibiotic is discussed in detail, from the stage of early safety testing in animals through phase I, II, and III clinical trials.

Drosophila and Galleria insect model hosts

“…The conventional methods of drug discovery involve either (a) computational selection of potential pathogen gene targets based on genome sequencing information and screening of chemical libraries for molecules that inhibit target gene function 52 or (b) screening of small molecule libraries for the capacity to induce a specific phenotype in purified protein targets or cultured cells; 53 subsequently, promising compounds are tested in vivo in mammalian hosts. Nevertheless, such host-free-based drug discovery methods are infrequently fruitful because they do not portray the complex and dynamic host-pathogen interactions that occur in vivo.…”

In Vitro Models to Study Hepatotoxicity

“…The development of new drugs consists of a variety of single steps leading from the discovery of pharmacological effects in cell and animal models to the assessment of toxicity and nally to the demonstration of ef cacy and safety in humans (46,90). Although the process that leads to the discovery of potent pharmacological effects has been reduced by rational drug designing in the past years, a variety of problems may occur in the preclinical and clinical development and lead to the failure of a compound.…”

Antibacterial activity of Saponaria officinalis and Zanthophyllum aramatum

“…They help in the treatment of different diseases and almost eradication of some diseases like tuberculosis.However, as time passes the handling of antibiotics in treatments of diseases increased, and the over usage provoked the development of resistance in bacteria (Siang Yong and Yvonne, 2015; Aminov, 2009). The development of resistance in microorganisms against antibiotics outpaced the development of new drugs (Gootz, 1990;Sum et al, 1999;Eliopolus, 2004;Jaswanthrai et al, 2013). The naturally occurring products are the main source for the indentifying and development of new antibiotics (Habich and Von Nussbaum, 2006).…”