A Review on Small Molecular Mimics of Antimicrobial Peptides with An Emphasis on Structure-Activity-Relationship Perspective

Abstract

A rapid emergence of antibiotic resistance in bacteria has brought forth an alarming situation in the face of public health, is a huge cause of concern around the globe. In addition, the biofilm forming ability of bacteria has further complicated the situation in the current scenario. To address this global clinical threats, small molecular mimics of antimicrobial peptides (AMPs) has emerged as a promising class of antibacterial agents, which kill the bacteria primarily by targeting their membrane and therefore bacteria find difficulties to develop resistance against them. Moreover, some of these class of molecules have already been reported as potent antibiofilm agents and showed promising in-vivo efficacy as well. In this review, we aim to provide an overview on this class of molecules with a focus on recent development in the field. Different class of small molecular AMP mimics are discussed with an emphasis on design rational and structure-activity-relationship (SAR) facet. The role of different parameters (such as hydrophobicity, charge, structural flexibility/rigidity, spatial distribution of hydrophobicity etc.) which control their physico-chemical property and thereby the antibacterial and toxicity are illustrated. Moreover, the antibiofilm ability as well as in-vivo efficacy of this class of molecules are described to elucidate the possibility for being developed as future antibacterial drugs. In the end, the challenges associated with this class of molecules for their clinical translation as antibacterial therapy are conferred along with future perspectives for further progression of the field.