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Jadimurthy, R.; Jagadish, S.; Nayak, S.C.; Kumar, S.; Mohan, C.D.; Rangappa, K.S. Phytochemicals as a Source of Antimicrobial Compounds. Encyclopedia. Available online: (accessed on 13 June 2024).
Jadimurthy R, Jagadish S, Nayak SC, Kumar S, Mohan CD, Rangappa KS. Phytochemicals as a Source of Antimicrobial Compounds. Encyclopedia. Available at: Accessed June 13, 2024.
Jadimurthy, Ragi, Swamy Jagadish, Siddaiah Chandra Nayak, Sumana Kumar, Chakrabhavi Dhananjaya Mohan, Kanchugarakoppal S. Rangappa. "Phytochemicals as a Source of Antimicrobial Compounds" Encyclopedia, (accessed June 13, 2024).
Jadimurthy, R., Jagadish, S., Nayak, S.C., Kumar, S., Mohan, C.D., & Rangappa, K.S. (2023, June 15). Phytochemicals as a Source of Antimicrobial Compounds. In Encyclopedia.
Jadimurthy, Ragi, et al. "Phytochemicals as a Source of Antimicrobial Compounds." Encyclopedia. Web. 15 June, 2023.
Phytochemicals as a Source of Antimicrobial Compounds

Many microorganisms develop resistance to drugs through different mechanisms, and this process is called antimicrobial resistance. It is highly essential to discover new antimicrobials to kill pathogenic microbes that have developed antimicrobial resistance. Natural sources, including plants, have been serving as a great source of medicinally important compounds for the past several decades.

antibacterial antifungal antiviral natural compounds phytocompounds

1. Introduction

Antimicrobial agents are drugs that are used to prevent and treat infections caused by bacteria, fungi, viruses, and parasites. Thousands of small molecules and peptides were isolated from natural sources such as plants, bacteria, fungi, and marine invertebrates, and some have demonstrated significant antimicrobial activity in preclinical settings and clinics [1][2]. Therefore, they have been used as standard antimicrobial drugs against microbial infections. The period between 1940 to 1965 is considered the golden era of antibiotics as many new antibiotics were introduced to modern medicine which revolutionized the treatment of bacterial infections [3]. Unfortunately, the phenomenon of antimicrobial resistance is becoming one of the primary health concerns across the globe, in which the pathogens do not respond to existing antimicrobial agents, which complicates the treatment regimen and thereby increases the mortality rate [4]. There is a swift spread of pan-drug-resistant bacteria at an alarming rate.
The World Health Organization (WHO) has declared that antimicrobial resistance is one of the top 10 global public health threats facing humanity. As per the antibiotic resistance threats report (2019) of the Centers for Disease Control and Prevention (CDC, the United States), the annual death rate due to antibiotic-resistant infection is over 35,000 people in the United States alone [5]. Misuse and overuse of antimicrobial agents are the prime reasons for the development of resistance by microbes, which pose a serious health concern to mankind [6][7].
Mother Nature is serving as a treasure house of medicinally important compounds that can be used against various human ailments, including cancer, malaria, inflammatory diseases, and microbial infections [8][9][10][11]. Extensive screening and research advancements in the previous century led to the discovery of thousands of bioactive secondary metabolites from medicinally important plants. Plants have been serving as a great source of bioactive compounds, which are being tested in preclinical disease models and clinical trials. Natural compounds, or their semi-synthetic derivatives obtained from plants, have contributed to the development of drugs against microbial diseases and various human ailments. For instance, artemisinin, a sesquiterpene lactone obtained from Artemisia annua, is used as a therapeutic agent for the treatment of malaria that is caused by Plasmodium falciparum. Various traditional medicine systems, folklore, codified systems of medicine, ethnopharmacology, ayurvedic classical texts, or zoopharmacognosy propose that some plants can be used against microbial infections. Some of the plant-derived metabolites have shown good antibacterial, antifungal, and antiviral activities in preclinical settings, and they can be considered potential candidates to be examined in clinical trials. 

2. Phytochemicals as a Source of Antimicrobial Compounds

2.1. Antibacterial Agents Derived from Plants

Among microbial infections, bacterial infections pose a huge threat to human life across the globe. The WHO has categorized bacterial pathogens into critical, high, and medium priority depending on the need to develop new drugs against drug-resistant bacteria. The bacteria that are grouped under critical priority encompass carbapenem-resistant-Acinetobacter baumannii and -Pseudomonas aeruginosa, carbapenem-resistant, and third-generation cephalosporin-resistant Enterobacteriaceae. The bacteria that are categorized as high priority include vancomycin-resistant Enterococcus faecium, methicillin-resistant, vancomycin-resistant-Staphylococcus aureus, clarithromycin-resistant Helicobacter pylori, fluoroquinolone-resistant Campylobacter spp., fluoroquinolone-resistant Salmonella spp., and third-generation cephalosporin-resistant, fluoroquinolone-resistant-Neisseria gonorrhoeae. The medium priority list comprises penicillin-non-susceptible Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, and fluoroquinolone-resistant Shigella spp. [12].

2.1.1. Apigenin

Apigenin is a flavonoid found in various plants, including Petroselinum crispum, Matricaria chamomilla, Apium graveolens, Basella rubra, Cynara scolymus, Origanum vulgare, and Portulaca oleracea [13]. It was found to have antibacterial activity against P. aeruginosa, K. pneumoniae, Salmonella typhimurium, Enterobacter aerogenes, and Proteus mirabilis. Apigenin was found to inhibit H. pylori-derived D-Alanine:D-alanine ligase with a relatively lesser IC50 value (132.7 μM) than a positive control D-cycloserine (299 μM). Apigenin displayed a binding affinity towards H. pylori-derived D-Alanine:D-alanine ligase (kD value: 22.3 μM), as demonstrated by surface plasmon resonance studies.

2.1.2. 18-β-Glycyrrhetinic Acid

Glycyrrhizic acid is the primary saponin found in Glycyrrhiza glabra L., of the licorice family [14]. Glycyrrhizic acid and its derivatives are endowed with antibacterial, antitumor, antiviral, antibacterial, and anti-inflammatory activities [15]. Notably, glycyrrhizic acid is metabolically inactive and thus, it is metabolized to 18-β-glycyrrhetinic acid by the intestinal microflora upon consumption, leading to its absorption into the bloodstream. It was demonstrated that 18β-glycyrrhetinic acid-induced bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and its topical application significantly reduced staphylococcal skin and soft tissue infection in mice models.

2.1.3. Honokiol

Honokiol [3′,5-di-(2-propenyl)-1,1′-biphenyl-2,2′-diol] is a bioactive neolignan found in the root bark of many species of the Magnoliaceae family, such as Magnolia officinalis, Magnolia obovata, and Magnolia grandiflora [16]. Honokiol has shown antibacterial potency against a wide range of bacteria from common oral pathogens to some of the ESKAPE organisms. Colistin is a last-line antibiotic that can be implemented in the treatment of multidrug-resistant (MDR) bacterial infections. Unfortunately, the emergence of mcr-1 (a plasmid-mediated colistin resistance gene) is threatening the clinical use of colistin [17]. Guo and colleagues demonstrated that honokiol enhances the sensitivity of MCR-1-positive Enterobacteriaceae infections to polymyxin (polypeptide antibiotics) in vitro and in vivo. Molecular dynamics simulations showed that honokiol establishes hydrogen bonding and hydrophobic interactions with the active region of MCR-1 [18].

2.1.4. Kaempferol

Kaempferol [3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] is a flavonol abundantly present in tea (Camellia sinensis), broccoli (Brassica oleracea), apple (Malus domestica), and strawberry (Fragaria x ananassa) [19]. It has also been reported to be found in medicinal plants, including Sophora japonica, Equisetum spp., Ginkgo biloba, and Euphorbia pekinensis [13]. The antibacterial activity and mechanism of action of kaempferol have been demonstrated in various studies. Kaempferol inhibits the PriA helicase (an enzyme crucial for the restart of DNA replication and bacterial survival) activity of S. aureus [20] and displayed efflux pump inhibition in S. aureus with an IC50 value of 19 µg/mL [21].

2.1.5. Naringin and Naringenin

Naringin (4′,5,7-trihydroxyflavanone-7-rhamnoglucoside) is a flavonoid glycoside that is excessively present in grapefruit and orange, whereas naringenin (5,7,4′-trihydroxyflavanone) is an aglycone form of naringin. Naringenin is effective against Enterococcus faecalis, a gram-positive bacterium present in the alimentary canal of humans and animals, which can cause life-threatening diseases in humans. Homology modeling and docking studies demonstrated that naringenin interacts with the active site of β-ketoacyl acyl carrier protein synthase Ⅲ, which is a key enzyme in the initiation of fatty acid synthesis in bacteria.

2.1.6. Nimbolide

Nimbolide (5,7,4′-trihydroxy-3′, 5′-diprenyl flavanone) is one of the vital limonoids present in the seeds, leaves, and flowers of Azadirachta indica, commonly known as neem [22]. It displayed bactericidal activity against H. pylori, a pathogen responsible for some diseases of the gastrointestinal tract, including peptic ulcers and gastric cancer. Merrell and colleagues demonstrated that neem oil extract possesses bactericidal activity [23]. Since A. indica has been reported to possess more than 300 phytochemicals, the same research group also demonstrated that nimbolide imparts bactericidal and antibiofilm activity against H. pylori [24].

2.1.7. Resveratrol

Resveratrol (3,4′,5,-trihydroxystilbene) is a naturally occurring phytoalexin and is present in red wine, grapes, peanuts, berries, etc. [25][26]. It has exhibited antibacterial properties against a variety of organisms including E. coli, vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus, Campylobacter species, and Vibrio species [27]. In an interesting study, the effect of resveratrol in combination with polymyxin B was examined against 50 MDR bacterial strains (26 strains of K. pneumoniae and 24 strains of E. coli), and among them, 44 strains were resistant to polymyxin B. Interestingly, resveratrol potentiated the antibacterial activity of polymyxin B against K. pneumoniae and E. coli [28]. Resveratrol has been reported to inhibit the electron transport chain and F0F1-ATPase, which contributes to the decline of ATP production and subsequent suppression of the growth of microorganisms [27]. It can also impart antibacterial activity by forming a copper-peroxide complex, upon which it interacts with DNA to form a DNA-resveratrol-copper ternary complex, which in turn ultimately results in the induction of DNA damage [29].

2.1.8. Sanguinarine

Sanguinarine is a benzophenanthridine alkaloid obtained from the rhizomes of Sanguinaria canadensis L. (bloodroot), Chelidonium majus L. (Celandine), Fumaria officinalis L. (Fumitory), and Bocconia frutescens L. (Plume poppy). In P. aeruginosa, glucose enters the cell through the OprB and OprB2 porins and enters the periplasmic space, where it can directly enter the cytoplasm through an ABC transporter or it can be metabolized, which subsequently transported from the periplasm to the cytoplasm through the KguT (2-ketogluconate transporter). It has been shown that the P. aeruginosa mutant that lacks 2-ketogluconate transporter was relatively less pathogenic than wild-type P. aeruginosa [30].

2.1.9. Withaferin A

Withaferin A (4-β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide) is a natural steroidal lactone present in Withania somnifera and other members of the Solanaceae family, such as Acnistus arborescens [31]. Withaferin A displayed effective antibacterial activity against P. aeruginosa with a MIC and MBC of 60 µM and 80 µM, respectively. The effect was mediated by damaging the bacterial cell membrane. In addition, a significant reduction in the level of ROS and lipid peroxidation was reported upon withaferin A administration in P. aeruginosa-infected zebra fish larvae [32]. Metallo-β-lactamases are the antibiotic inactivating enzymes that contribute to the resistance against carbapenems. New Delhi metallo-β-lactamase (NDM-1) is contributing greatly to the emergence of antibiotic resistance among ESKAPE pathogens.

2.2. Antifungal Agents Derived from Plants

Fungal infections in humans can be considered one of the low-key maladies in the antimicrobial research and healthcare sectors. Medical interventions (such as the use of catheters, intravascular or intracranial devices, neurosurgical procedures, the usage of contaminated devices, and the overuse of broad-spectrum antibiotics), treatment-associated immunosuppression (organ transplantations or stem cell transplantations), disease-associated immunosuppression (HIV infection), and co-infections (tuberculosis) are the risk factors abetting the fungal infections in humans [33]. COVID-19-associated fungal infections, such as mucormycosis, aspergillosis, and candidaemia, are recent examples of co-infections. Fungal infections are annually causing around 1.6 million deaths, which is higher than the deaths caused by tuberculosis (1.5 million deaths/year) [34][35].

2.2.1. Carvacrol

Carvacrol (5-isopropyl-2-methylphenol) is a major constituent of essential oils obtained from the Lamiaceae family of plants, such as thyme and oregano [36]. Investigations carried out by Ahmed et al., (2011) showed the fungicidal activity of carvacrol against the various strains of fluconazole-sensitive and -resistant candida species, such as C. albicans, C. tropicalis, C. parapsilosis, C. krusei, and C. glabrata (mean MIC values of 75–90 mg/L for fluconazole-sensitive candida species and 75–100 mg/L for fluconazole-sensitive candida species) [37]. The study also suggested that the fungicidal activity of carvacrol could be due to interference with ergosterol biosynthesis and disruption of membrane integrity. Rao et al., showed that carvacrol disrupts Ca2+ and H+ homeostasis in Saccharomyces cerevisiae. Transcriptional profiling post-exposure to carvacrol showed a robust transcriptional response closely resembling that of calcium stress. It was speculated that the antifungal activity of carvacrol could be due to the induction of Ca2+ stress and inhibition of the TOR signaling pathway [37].

2.2.2. Emodin

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a secondary metabolite produced by plants, such as Senna alata, Rumex abyssinicus, Odontites serotina, Reynoutria japonica, polygonum spp., and Rheum palmatum [38][39]. It possesses a therapeutic potential against many human ailments, such as hepatitis, cancer, arthritis, cholelithiasis, Alzheimer’s disease, ulcerative colitis, pancreatitis, asthma, and many bacterial and viral infections [40]. The antifungal activity of emodin against C. albicans (MIC: 12.5 μg/mL) was demonstrated [41]. Emodin showed antibiofilm activity and inhibition of hyphal formation in C. albicans cells [42]. Emodin also inhibited 50% total kinase activity of C. albicans at concentrations beginning from 0.5 µg/mL [42].

2.2.3. Eucalyptol

Eucalyptol [1,8-Cineole (1,3,3-trimethyl-2-oxabicyclo [2.2.2]acetate)] is a major component of essential oils extracted from plants of Eucalyptus species, such as Eucalyptus smithii, Eucalyptus globules, etc. It is also obtained from the essential oils of other plants, such as tea trees, mugwort, rosemary, etc. [43]. Eucalyptol showed antifungal activity against C. albicans and C. glabrata (MIC90 value: 800 μg/mL) by increasing ROS generation, G1/S phase arrest, elevating membrane permeability, and disrupting mitochondrial membrane potential [44]. Gene expression analysis revealed that genes essential for hyphal cell wall protein (HWP1), secreted aspartyl proteinase (SAP1), and cell surface adhesion (ALS1) are downregulated [44].

2.2.4. Eugenol

Eugenol (2-methoxy-4-[2-propenyl] phenol) belongs to the class of phenylpropanoids and is present in the essential oils obtained from Cinnamomum and clove [45]. Pereira et al., (2013) studied the antifungal activity of eugenol against Trichophyton rubrum, which is responsible for causing dermatophytosis [46]. Eugenol inhibited the growth of different strains of T. rubrum with MIC values ranging from 64–512 µg/mL. The inhibitory growth activity was found to be mediated by causing membrane abnormalities, which include short, twisted hyphae and a reduction in conidia formation [46]. In another study, eugenol was reported to impart antifungal activity against C. albicans by inhibiting the synthesis of ergosterol, inducing oxidative stress, promoting lipid peroxidation, and increasing membrane permeability [47]. Similarly, eugenol displayed antifungal activity against clinical isolates of C. glabrata (MIC value: 128 μg/mL) by the inhibition of biofilm formation [48].

2.2.5. Geraniol

Geraniol (3,7-dimethylocta-trans-2,6-dien-1-ol) is a monoterpene alcohol and a major constituent of essential oils extracted from wild bergamot, rose, lavender, palmarosa, etc. [49]. Geraniol is commercially used as a fragrance material in deodorants and cosmetic products. It is reported to have anticancer activity against murine leukemia, hepatoma, and melanoma cells. Miron et al., (2014) studied the antifungal activity of geraniol against many dermatophytes (Trichophyton mentagrophytes, T. rubrum, Microsporum canis, and Microsporum gypseum) and yeasts (C. albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis, C. neoformans, Trichosporon asahii) [50]. Geraniol demonstrated potent antifungal activity against Microsporum strains and other dermatophytes with GMIC values of 19.5 and 25.4 µg/mL, respectively [50]. It also displayed moderate antifungal activity against yeasts compared to dermatophytes. The investigation of the mechanism of action of the antifungal properties of geraniol against T. asahii revealed the ability of binding of geraniol to ergosterol and subsequent membrane destabilization [50].

2.2.6. Hibiscuslide C

Hibiscuslide C (1-formyl-2, 8-dihydroxy-7-methoxy-6-methylnaphthalene) is a phytochemical reported to be present in plants, such as Hibiscus taiwanensis and Abutilon theophrasti [51]. Hibiscuslide C showed antifungal activity against C. albicans, C. parapsilosis, Trichosporon beigelii, and Malassezia furfur, with MIC values of 5, 5–10, 10, and 5 µg/mL, respectively [51]. The mechanism of antifungal property of hibiscuslide C against C. albicans was found to be due to its involvement in membrane disruptive mechanisms, such as membrane depolarization and pore formation [51].

2.2.7. Magnoflorine

Magnoflorine is a phytochemical present in medicinal plants, such as Phellodendron amurense, Sinomenium acutum, Thalictrum isopyroides, Magnolia officinalis, and Berberis kansuensis. It is reported to possess many pharmacological properties, such as antidiabetic, anti-inflammatory, immunomodulatory, antioxidant, and antifungal activities [52]. Magnoflorine displayed antifungal activity against various Candida strains, such as C. albicans C. tropicalis, C. parapsilosis, and C. glabrata [53].

2.2.8. Tea Saponin

Tea saponin is a phytochemical that belongs to an oleanane-type pentacyclic triterpene that is distributed in plants, such as Camellia oleifera and Camellia sinensis [54]. Tea saponin is present in the seed cake, which is obtained as the byproduct during the extraction of oil from tea or camellia seeds. Tea saponin is a natural surfactant used extensively in the food, chemical, pesticide, and cosmetic industries. Tea saponin is endowed with many pharmacological properties, such as antimicrobial, anti-inflammatory, antioxidant, and antiallergic properties [55].

2.3. Antiviral Agents Derived from Plants

2.3.1. Betulinic Acid

Betulinic acid is a pentacyclic lupane-type triterpenoid widely present in different plant species [56]. It is generally isolated from the Birch tree (Betula sp., Betulaceae), which has well-known medicinal applications. Betulinic acid is also present in plants belonging to the genera Ziziphus, Syzygium, Diospyros, and Paeonia [57]. Many investigations revealed the antiviral potency of betulinic acid against different viruses. The antiviral function of betulinic acid against influenza A/PR/8 virus-infected A549 (human lung cancer) cells was examined [58]. Betulinic acid (50 µM) displayed good antiviral activity (98%) against the influenza A/PR/8/34 virus in A549 cells without significant cytotoxicity towards host A549 cell lines. Betulinic acid (10 mg/kg/dose for seven days) administration attenuated pulmonary pathological symptoms, including necrosis, number of inflammatory cells, and pulmonary edema in influenza A/PR/8/34 virus-infected C57BL/6 mice [58].

2.3.2. Guggulsterone

Guggulsterone is a phytosteroid present in the plant Commiphora gileadensis (L.), which is generally known as the “balsam of Mecca” [59]. C. gileadensis is known for its usage in the traditional Arabian medicinal system to treat urinary retention, jaundice, constipation, inflammatory disorders, and liver disorders [59]. This compound is also reported to be present in the plant Guggul tree (Commiphora mukul), and its medicinal values are well-documented in Ayurveda, a traditional Indian medicinal system [60]. Bouslama et al., (2019) studied the antiviral effect of methanolic extract of C. gileadensis leaves on two enveloped viruses (herpes simplex virus type 2 and respiratory syncytial virus type B) and two nonenveloped viruses (coxsackie virus B type 3 and adenovirus type 5). Methanolic extract of C. gileadensis leaves showed antiviral activity against enveloped viruses with an IC50 and a selectivity index of approximately 20 µg/mL and >10, respectively [59]. Subsequent bio-guided assays revealed that the leaf extract contains guggulsterone as the active compound.

2.3.3. Salvianolic Acids

Salvianolic acids are the class of phytochemicals present in Salvia miltiorrhiza (Danshen). The medicinal properties of S. miltiorrhiza have been recorded in traditional Chinese medicine and it has been known to promote blood circulation. S. miltiorrhiza contains about 10 different salvianolic acids and all of them have a common core chemical structure known as Danshensu [(R)-3-(3,4-Dihydroxyphenyl)-2-hydroxypropanoic acid] [61]. Out of these types, salvianolic acids A, B, and C are reported to have antiviral activity against SARS-CoV-2. Salvianolic acids demonstrate antiviral activity by binding to the SARS-CoV-2 spike (S) protein [62]. S protein is present on the surface of SARS-CoV-2 and interacts with angiotensin-converting enzyme 2 (ACE2), which is present in the host cells, to mediate the viral entry into the cells.

2.3.4. Silvestrol

Silvestrol (cyclopenta[b]benzofuran flavagline) is a secondary metabolite present in the species belonging to the Aglaia genus, and it is reported to have broad-spectrum antiviral activity against different viruses. Silvestrol imparts an antiviral function against the Ebola virus by inhibiting viral replication [63]. Silvestrol induces antitumor activity by binding to the eIF4A subunit of the eIF4F complex and thereby attenuates the translation of oncoproteins, such as c-MYC and PIM-1. The eIF4F complex contributes to the scanning of the 5′ untranslated region (UTR) of mRNA and the recognition of start codons by the ribosome to initiate translation. During Ebola infection, the virus delivers its RNA into the host cells, where viral transcription is initiated using it as a template.

3. Synergistic Antimicrobial Effects of Plant Metabolites with Standard Antibiotics

The percentage of FDA-approved plant-derived antimicrobials is very insignificant (around 3%) compared to the abundance of plant metabolites [64]. Many traditional plant extract-based therapies involve the administration of a complex mixture of different phytochemicals that work in unison and may contribute to the synergistic effect to combat the growth of infectious microorganisms. Some researchers strongly believe that the synergistic potential of plant extract-based therapy might be a promising approach to address the rising antibiotic resistance [65]. In support of this, several plant-derived compounds have been demonstrated to potentiate the effect of antibiotics that are in clinical practice [66]. For instance, piperine, present in the Piper nigrum and Piper longum, inhibits bacterial efflux pumps to impart antibacterial activity. The nanoliposomes co-loaded with gentamicin and piperine showed synergistic antibacterial activity against MRSA and also reduced the MIC value of gentamicin about 32-fold [67].Similarly, chanoclavine isolated from Ipomoea muricata also displayed bacterial efflux inhibition and presented a synergistic activity with tetracycline against MDR E. coli with a 16-fold reduction in the MIC of tetracycline [68]. Tomatidine, a secondary metabolite derived from the plants of tomato, potato, and eggplant also demonstrated a synergistic effect with several aminoglycoside antibiotics against the MDR of S. aureus [69]. Thymol, a component of essential oil obtained from Thymus vulgaris and Origanum vulgare, displayed synergism with fluconazole against clinical isolates of Candida species such as C. albicans, C. glabrate, and C. krusei [70]. Epigallocatechin gallate (EGCG), a polyphenol present in tea leaves showed synergistic antifungal activity with antimycotics such as miconazole, fluconazole, and amphotericin B against many Candida species [71]. These reports suggest that natural compounds obtained from plants can be used as potentiating agents of antimicrobial activity and this fact can be considered in clinical trials.

4. Plant-Derived Drugs that are in Clinical Practice for the Treatment of Human Ailments

Plants serve as an arsenal of secondary metabolites and their therapeutic applications against many infectious diseases are well-documented in ancient medical texts and paleobotanical findings at archeological sites [72][73]. Approximately 3% of natural products obtained from plants are approved by FDA as antimicrobial agents and an extensive portion of FDA-approved natural antimicrobial agents are obtained from microbes [74]. But these reports may not reflect the true potential of phytochemicals as antimicrobial agents. According to the WHO, around 80% of the developing world is dependent on traditional medicine derived from medicinal plants [75]. In support of this, a huge number of drugs obtained from plants are in today’s clinical practice. Artemisinin, a phytochemical isolated from Artemisia annua, is widely used for the treatment of malaria, a life-threatening disease caused by Plasmodium falciparum. The discovery of artemisinin from plants is a breakthrough event research arena of plant-derived antimicrobial compounds. Apart from antimicrobials, many plant-derived compounds have also been developed as drugs against many human diseases. Approximately around 25-28% of modern medicines are derived from plant sources [76]. For instance, galantamine, an isoquinoline alkaloid present in the Galanthus nivalis and Galanthus woronowii acts as an acetylcholinesterase inhibitor and is used in the treatment of Alzheimer’s disease [77][78]. Nitisinone is a chemical derivative of leptospermone, a phytochemical present in the plant Callistemon citrinus. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase and it is used in the treatment of hereditary tyrosinemia type 1 [79]. Taxol, a blockbuster anticancer drug, was initially isolated from the bark of Taxus brevifolia and subsequently demonstrated to be also produced by endophytes. Camptothecin is an approved drug that imparts an anticancer effect by inhibiting topoisomerase I and was initially identified to be produced by Camptotheca acuminate. Similarly, curcumin is a polyphenol present in the Curcuma longa and its medicinal applications are mentioned in ancient texts such as traditional Indian medicine and traditional Chinese medicine. It is considered a promising chemo-preventive agent against skin diseases such as psoriasis, vitiligo, and melanoma [80]. Curcumin is also reported to possess good antibacterial activity against different pathogenic microorganisms [81]. These examples provide a glimpse of the diverse therapeutic potential of phytochemicals. The logical drug repurposing approach also serves as an alternative approach for the determination of the antimicrobial activity of plant-derived drugs that are used against other diseases.

5. Conclusion and Future Perspectives

Antimicrobial resistance is one of the most serious health concerns across the globe as many pathogens are rapidly developing resistance against existing antimicrobials. In the current day scenario, there is no effective therapeutic agent with the potential to reverse antimicrobial resistance and many leading laboratories are extensively working to discover new antimicrobials. Plant-based natural compounds are relatively less studied in the context of developing antimicrobial drugs. Natural compounds have been of great interest in the drug discovery process due to their structural diversity, chemical novelty, abundance, and bioactivity. Natural compounds have been isolated from various organisms including bacteria, fungi, invertebrates, marine creatures, and plants. All of them have enormously contributed to the development of drugs against various human ailments. For instance, doxorubicin, bleomycins, epothilones, paclitaxel, camptothecin, podophyllotoxins, and vinca alkaloids are some of the well-known drugs derived either from bacteria, fungi, and plants [82][83][84]. In 2000, it was estimated that 57% of compounds that were undergoing clinical trials for cancer treatment are natural compounds [83]. It may be noted that plant-derived metabolites have displayed antimicrobial activity against drug-resistant microorganisms as discussed in the present article. A comprehensive investigation of the antimicrobial functions of plant metabolites needs to be carried out to explore their therapeutic potential. The plant metabolites can also be considered as scaffolds or template structures to chemically derivatize them to obtain compounds with improved antimicrobial efficacy. Additionally, the role of phytogenous compounds needs to be examined along with standard antibiotics to explore the possible synergistic effects. Overall, some plant metabolites have demonstrated good antimicrobial effects on clinically important microbes and they could serve as future drugs against MDR pathogens.


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