Membrane-Active Small Molecules: Designs Inspired by Antimicrobial Peptides

Abstract

Infectious diseases continue to be one of the major contributors to human morbidity. The rapid rate at which pathogenic microorganisms have developed resistance against frontline antimicrobials has compelled scientists to look for new alternatives. Given their vast antimicrobial repertoire, substantial research effort has been dedicated toward the development of antimicrobial peptides (AMPs) as alternative drugs. However, inherent limitations of AMPs have driven substantial efforts worldwide to develop synthetic mimics of AMPs. This review focuses on the progress that has been made toward the development of small molecules that emulate the properties of AMPs, both in terms of design and biological activity. Herein we provide an extensive discussion of the structural features of various designs and we examine biological properties that have been exploited. Furthermore, we raise a number of questions for which the field has yet to provide solutions and discuss possible future research directions that remain either unexploited or underexploited.

Keywords: antibiotics; antiprotozoal agents; antiviral agents; drug design; peptidomimetics.