Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery

Abstract

The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated. While many studies have tried to summarize NPs with antibacterial activities, a comprehensive review with rigorous selection criteria has never been performed. In this work, the literature from 2012 to 2019 was systematically reviewed to highlight plant-derived compounds with antibacterial activity by focusing on their growth inhibitory activity. A total of 459 compounds are included in this Review, of which 50.8% are phenolic derivatives, 26.6% are terpenoids, 5.7% are alkaloids, and 17% are classified as other metabolites. A selection of 183 compounds is further discussed regarding their antibacterial activity, biosynthesis, structure-activity relationship, mechanism of action, and potential as antibiotics. Emerging trends in the field of antibacterial drug discovery from plants are also discussed. This Review brings to the forefront key findings on the antibacterial potential of plant NPs for consideration in future antibiotic discovery and development efforts.

Figure 1.

A) Chemical classes of alkaloids investigated for antibacterial activity and B) top ten plant families yielding antibacterial alkaloids under the study parameters.

Figure 2.

A) Chemical classes of phenolic derivatives investigated for antibacterial activity and B) top ten plant families yielding antibacterial phenolic derivatives.

Figure 3.

A) Chemical classes of terpenoids investigated for antibacterial activity and B) top ten plant families yielding antibacterial terpenoids.

Figure 4.

A) Chemical classes of other metabolites investigated for antibacterial activity and B) top seven plant families yielding other antibacterial metabolites. The remaining 20 plant families had less than three compounds each represented in the data.

Figure 5.

Mean and standard deviation of minimum inhibitory concentration (MIC) of compounds for each of the four chemical classes, with significant differences in MIC values (μg/mL) for A) all bacteria; B) gram-positive bacteria and C) gram-negative bacteria. P-values: *: P < 0.05, **: P < 0.01, *** P < 0.001, **** P < 0.0001.

Figure 6.

Minimum inhibitory concentration (MIC) of compounds reported by chemical class, with significant differences in MIC values for A) Staphylococcus aureus, B) Escherichia coli, C) all drug resistant strains of Staphylococcus aureus, D) Bacillus subtilis, E) Pseudomonas aeruginosa, and F) Klebsiella pneumoniae. No significant difference was observed between the chemical classes for each bacterium.

Figure 7.

The most targeted A) bacterial genera and B) bacterial species by antibacterial plant compounds.