Bifunctional antibiotic hybrids: A review of clinical candidates

Augustine Jing Jie Koh; Varsha Thombare; Maytham Hussein; Gauri G Rao; Jian Li; Tony Velkov

doi:10.3389/fphar.2023.1158152

Bifunctional antibiotic hybrids: A review of clinical candidates

Front Pharmacol. 2023 Jun 12:14:1158152. doi: 10.3389/fphar.2023.1158152. eCollection 2023.

Authors

Augustine Jing Jie Koh¹, Varsha Thombare², Maytham Hussein², Gauri G Rao³, Jian Li⁴, Tony Velkov^{1

2}

Affiliations

¹ Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIP, Australia.
² Monash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Parkville, VIP, Australia.
³ Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
⁴ Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Parkville, VIP, Australia.

Abstract

Antibiotic resistance is a top threat to human health and a priority across the globe. This problematic issue is accompanied by the decline of new antibiotics in the pipeline over the past 30 years. In this context, an urgent need to develop new strategies to combat antimicrobial resistance is in great demand. Lately, among the possible approaches used to deal with antimicrobial resistance is the covalent ligation of two antibiotic pharmacophores that target the bacterial cells through a dissimilar mode of action into a single hybrid molecule, namely hybrid antibiotics. This strategy exhibits several advantages, including better antibacterial activity, overcoming the existing resistance towards individual antibiotics, and may ultimately delay the onset of bacterial resistance. This review sheds light on the latest development of the dual antibiotic hybrids pipeline, their potential mechanisms of action, and challenges in their use.

Keywords: antibiotic pipeline; antibiotic resistance; drug combinations; drug synthesis; hybrid antibiotics.

Publication types

Review

Grants and funding

GR, TV, and JL are supported by the National Institute of Allergy and Infectious Diseases, award number R01AI146241. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TV is an MPT Connect REDI Fellow. JL is a National Australian Health and Medical Research Council Senior Principle Research Fellow.