Plant natural products for antibacterial drug development against ESKAPE pathogens

Antibiotic resistance is considered a global health emergency as resistance towards existing antibacterial agents is developing drastically. More specifically, a few groups of bacterial pathogens are posing a threat to public health; thus, these pathogens are grouped as the ESKAPE pathogens- Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Several efforts are being made to discover and develop a new class of antibacterial drugs to combat the resistance of these pathogens. Natural products from bacterial sources have dominated the clinically used antibiotics, as these compounds possess comparatively complex chemical structures. Similarly, natural compounds from plant sources exhibit diverse chemical structures, and several compounds have shown excellent antibacterial activities. Moreover, these plant-natural compounds demonstrate very good antibacterial efficacy in drug or multidrug-resistant (MDR) strains of bacterial pathogens. However, most of the compounds are limited to early-stage drug development processes only. Thus, in this article, we discuss chemical diversity, antibacterial activity towards various pathogens, and limitations for late-stage drug development of natural compounds from plant sources. The chemical scaffold diversity of these natural compounds offers an opportunity for medicinal chemists to navigate these early hits to the preclinical stage through lead optimization based on complex chemistry. Furthermore, a perspective on opportunities and challenges is also presented on plant natural compounds in antibacterial drug discovery. • Antimicrobial resistance is a global health emergency • ESKAPE bacterial pathogens develop antibiotic resistance rapidly • Natural compounds from plant sources exhibit broad chemical diversity • Natural compounds show excellent antibacterial activity • Natural compounds serve as magnificent scaffolds for medicinal chemists