Plants have two major groups of metabolites: primary and secondary. Carbohydrates and lipids are products of the primary metabolism of plants, while phenolic compounds, carotenoids, alkaloids, saponins, and terpenoids are considered to be secondary metabolites. Numerous secondary metabolites exhibit multifaceted pharmacological properties, such as anti-inflammatory, antitumor, antioxidant, and antimicrobial activities, among others.
1. Phenolic Compounds
Known for providing protection to plants against microbial agents, oxidants, and ultraviolet radiation, phenolic compounds are characterized by the presence of a benzoic ring in their chemical structure
[1]. Currently, more than 8000 phenolic compounds with some bioactivity have been categorized
[2], including phenolic acids and aldehydes, flavonoids, chalcones, benzophenones, xanthones, stilbenes, benzoquinones, and polyphenols, among others, which can be extracted from different parts of the plant, such as the leaves, roots, and fruits (bark and seeds)
[3]. Studies indicate that these compounds are more effective against Gram-positive bacteria, which can be explained by the presence of the thick layer of peptidoglycan and the absence of an external membrane found in Gram-negative bacteria, which exert a hydrophobic action, preventing the penetration of hydrophilic molecules into the bacterial cell, such as phenolic compounds
[1]. The main mechanism of action of phenolic compounds is related to their ability to reduce the expression of efflux pumps
[4]. However, there are reports of molecules from this group that inhibit DNA gyrase and, thus, are capable of inhibiting microbial growth, as is the case for tannins
[5] and anthraquinones
[6]. Poomanee et al.
[7] found promising results of the antimicrobial action of phenolic compounds extracted from the seeds of
Mangifera indica against standard strains of
Staphylococcus aureus and
Staphylococcus epidermidis. Similarly, Lyu et al.
[8] found that phenolic compounds from extracts of
Hibiscus acetosella inhibited the growth of
S. aureus, in addition to being effective in the microbial control of
P. aeruginosa. Baicalein, a flavonoid isolated from the roots of
Thymus vulgaris,
Scutellaria baicalensis, and
Scutellaria lateriflora, has shown good antimicrobial activity against viral and bacterial isolates
[9]. Another study demonstrated that the compound baicalein increased the susceptibility of methicillin-resistant
S. aureus (MRSA) to beta-lactams, tetracycline, and ciprofloxacin through the inhibition of efflux pumps
[10]. Within this group, it is still worth highlighting the chalcones, which can impede microbial growth by inhibiting the expression of efflux pumps. This is the case of the 4′,6′-dihydroxy-3′,5′-dimethyl-2′-methoxylic chalcone isolated from
Dalea versicolor, which showed good antimicrobial action against
S. aureus, being able to inhibit the expression of the
NorA efflux pump
[11].
2. Alkaloids
The term alkaloid means “similar to alkalis”, referring to the basic or alkaline character of the substances. About 12,000 alkaloid compounds isolated from plant extracts have already been categorized, with various medicinal actions, such as antitumor, analgesic (morphine and codeine), and antimicrobial properties
[12]. They present a chemical structure with heterocyclic rings containing N-heterocyclic nitrogen and can be classified according to their carbon precursors and structure
[1]. Examples of alkaloid compounds commonly found in plants include pyridine, piperidine, quinoline, alkaloidal amines, and terpenoid
[13]. The antibacterial action of the alkaloid fractions isolated from
Callistemon citrinus leaves was demonstrated against Gram-positive and Gram-negative bacterial isolates, such as
S. aureus and
P. aeruginosa, by Mabhiza et al.
[14]. The authors believe that the compound acted by inhibiting the transport of ATP-dependent substances across the bacterial cell membrane. Liu et al.
[15] identified the good antimicrobial action of benzyltetrahydroisoquinolin-derived alkaloids from the leaves of
Doryphora aromatica against isolates of
Mycobacteria spp. and
S. aureus resistant to methicillin. Pech-Puch et al.
[16] verified the good (MIC in the range of 1–8 µg/mL) and moderate (MIC value of 16 µg/mL) antimicrobial action of diterpene alkaloids from
Agelas citrina against the Gram-positive pathogens
S. aureus,
S. pneumoniae, and
E. faecalis and the Gram-negative pathogens
A. baumannii,
P. aeruginosa, and
K. pneumoniae,. Reserpine is an indole alkaloid isolated from the
Rauwolfia serpentinaa species of flower in the Apocynaceae family, native to the Asian continent, which has been shown to increase the susceptibility of multidrug-resistant clinical isolates of
A. baumannii and
S. maltophilia [17][18].
3. Saponins
Saponins can be found in a variety of plants and are chemically characterized by the presence of glycosylated groups, formed by a hydrophilic and a lipophilic part. This structure confers the properties of detergents and surfactants on saponins
[1][19]. One of the reported properties of saponins is antimicrobial activity. It is known that the chemical structure of these compounds directly interferes with the effectiveness of their antimicrobial action. There have been reports that saponins with trisaccharide chains exhibited good antifungal action, whereas saponins with mono- or disaccharide chains did not show good antimicrobial action
[20]. Lunga et al.
[21] observed the promising antimicrobial action of different saponins from
Paullinia pinnata against Gram-positive and Gram-negative bacteria, as well as yeast. From
Cephalaria ambrosioides, some triterpenoid saponins, cauloside A, α-hederin, dipsacoside B, and sapindoside B were isolated, showing strong anti-bacterial activity against
S. aureus,
S. epidermidis,
P. aeruginosa,
E. coli,
E. cloacae, and
K. pneumoniae (MIC values 1.80–2.50 µg/mL)
[22].
4. Terpenoids
Terpenoids, or terpenes, are a class of metabolites that encompass a variety of natural substances, which have in common the presence of C
5 isoprene units in their chemical structure. Depending on the amount of C
5 isoprene involved in their synthesis, terpenes can be classified as monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, and triterpenoids. More than 40,000 terpenoid substances are known, with different applications: aromatic, pharmaceutical, agricultural, and industrial
[1]. In addition, there are reports of the promising antimicrobial action of different types of terpenes. For example, Biva et al.
[23] demonstrated the antibacterial action of terpene compounds from
Eremophila lucida against
S. aureus isolates. Similarly, Gartika et al.
[24] observed that terpenoids obtained from
Myrmecodia pendans showed promising antibacterial action against
S. mutans—an important caries-related pathogen—in addition to being effective in inhibiting and eradicating
S. mutans biofilm. Zhu et al.
[25] isolated and identified terpenoids from
Commiphora resin, with good antibacterial action against sensitive and resistant isolates of
Mycobacterium tuberculosis.
5. Other Compounds
Many phytochemicals not mentioned above have been found to exert antimicrobial properties, including mucilage, essential oils, fixed oils, sterols, and waxes. Lipids are a class of naturally occurring compounds that include essential oils, fixed oils, sterols, waxes, phospholipids, and fat-soluble vitamins. They were once categorized as primary metabolites, but studies have shown them to have secondary metabolite functions
[26]. While carbohydrates are classified as primary metabolites, specific carbohydrates have been discovered to have functional properties and are categorized as secondary metabolites, such as mucilage, which is produced as a phytochemical by a variety of plants and exhibits a wide range of biological activities
[27]. Some secondary metabolites, on the other hand, are made mostly by regulators that are activated by certain carbohydrates
[28]. Moreover, a published report showed the antibacterial activity present in garlic and onions, which exhibit inhibitory effects on diverse microorganisms due to their abundant sulfoxide contents, which impart them with antimicrobial properties. On the other hand, the horseradish, mustard seeds, and wasabi demonstrate inhibitory activity, attributed to their elevated levels of allyl glucosinolates
[29].