*2.2. Non-Flavonoids*

Phenolic acids (benzoic, phenylacetic, and phenylpropionic acids) have been found to inhibit pathogenic and non-pathogenic bacteria and fungi such as *Escherichia coli, Lactobacillus* spp., *S. aureus*, *Pseudomonas aeruginosa* and *Candida albicans* [26]. Hydroxycinnamic acids (caffeic, coumaric, ferulic, and sinapic acids) have been found to inhibit *Bacillus cereus* and *S. aureus*; *P. fluorescens* [27]. In addition, the antibacterial activity of caffeic, ferulic, and p-coumaric acids against *E. coli*, *S. aureus*, and *B. cereus*, with p-coumaric acid being effective against *E. coli*, has been reported [27]. Hydroxycinnamic acids (i.e., nitrobenzoate, p-aminobenzoate, ethyl aminobenzoate, ethyl- and methyl-benzoate, salicylic acid, transcinnamic acid, trans-cinnamaldehyde, ferulic acid, o-acetoxy benzoic acid, and anthranilic

acid) have been found to inhibit aflatoxins production from *Aspergillus flavus* and *Aspergillus parasiticus* [28]. Additionally, furocoumarins present in carrots, celery, citrus fruits, parsley, and parsnips have been reported for their antimicrobial activity against *E. coli* O157:H7, *Erwinia carotovora*, *Listeria monocytogenes*, and *Micrococcus luteus* [29].

The antibacterial properties of some common foods and beverages such as coffee against *Legionella pneumophila* and *E. coli* O157:H7 are attributed to its compounds such as caffeic acid, chlorogenic acid, and protocatechuic acid [30,31]. Furthermore, tea (*Camellia sinensis*) has also been found to display antimicrobial properties [32–34] through its predominant catechin, epigallocatechin gallate, against methicillin-resistant *S. aureus* (MRSA). The compound E-cinnamaldehyde has been found to significantly contribute to the antimicrobial properties of cinnamon stick extract (Ext) against *B. cereus, E. coli, L. monocytogenes, S. aureus,* and *Salmonella* [35].

### *2.3. Extraction of Polyphenols from Plant Products*

Extraction methods have been developed recently using modern technology. These methods use fewer or no organic solvents, thereby minimizing environmental and health impacts and maximizing the yield of desired polyphenols by selective extraction [36]. Advanced methods such as microwave-assisted, ultrasound-assisted, pulsed -electric-fieldassisted and enzyme-assisted extractions, as well as pressurized liquid and supercritical fluid extractions, are given prime importance these days to extract desired polyphenols from the plant products [37,38]. One of the recent studies has suggested extraction of non-extractable or bound polyphenols by pretreatment using the aforementioned methods, which are further cleaved using acid, alkaline, or enzyme treatments, followed by purification step using solid-phase extraction column chromatography and finally storage step using lyophilization [39]. Studies have illustrated that the bioavailability and yield of polyphenols are one of the most important factors of their antimicrobial activity [40,41]. However, along with these factors, their structure has also been found to play a critical role in their antimicrobial activity [42,43]. The relationship between the structure of polyphenols and their antimicrobial activity is elaborately illustrated in the proceeding section.

#### **3. Antimicrobial Activity and Structural Relationship of Plant-Derived Polyphenols**

The structural diversity of polyphenols is immense, and the impact of antimicrobial action they produce against microorganisms depends on their structural configuration [44]. For instance, Phenolic acids inhibit the activity of bacterial enzymes, disrupting their metabolism and depriving the substrates necessary for growth. The hydroxycinnamic acids (p-coumaric acid, caffeic, and ferulic acid) induced higher ion leakage and a more significant influx of protons into the cells, compared with hydroxybenzoic acids, gallic, vanillic, and syringic acid [45]. Additionally, these hydroxycinnamic acids have been found to meet Lipinski's rules, proving their functional potential as drugs and antimicrobial agents. The relationship between chemical structure and biological activity has received considerable attention in recent years because it allows the prediction of chemical toxicity or bioactivity without an inordinate amount of time and effort.

The potency of an antimicrobial is attributed to its structural characteristics. The relationship of the antimicrobial activity of plant polyphenols is classified into four types: (1) position of functional groups (FNG), (2) number of FNG, (3) presence of C2=C3 double bond, and (4) type of FNG.

### *3.1. Position of Functional Group*

The structural antimicrobial activity of the major plant polyphenols, i.e., flavonoids, is well documented [46]. The amphipathic features of flavonoids play an essential role as far as antibacterial properties are concerned [47]. The hydrophobic substituents such as prenyl groups, alkylamino chains, alkyl chains, and nitrogen or oxygen-containing heterocyclic moieties usually enhance the antibacterial activity of all flavonoids [48]. Different classes of flavonoids, mainly chalcones, flavanes, and flavan-3-ol exhibits better antimicrobial activity due to variation in the position of the functional group attached to the rings [46].
